Ileitis-associated tertiary lymphoid organs arise at lymphatic valves and impede mesenteric lymph flow in response to tumor necrosis factor.

Lymphangitis and the formation of tertiary lymphoid organs (TLOs) in the mesentery are features of Crohn's disease. Here, we examined the genesis of these TLOs and their impact on disease progression. Whole-mount and intravital imaging of the ileum and ileum-draining collecting lymphatic vessels (CLVs) draining to mesenteric lymph nodes from TNFΔARE mice, a model of ileitis, revealed TLO formation at valves of CLVs. TLOs obstructed cellular and molecular outflow from the gut and were sites of lymph leakage and backflow. Tumor necrosis factor (TNF) neutralization begun at early stages of TLO formation restored lymph transport. However, robustly developed, chronic TLOs resisted regression and restoration of flow after TNF neutralization. TNF stimulation of cultured lymphatic endothelial cells reprogrammed responses to oscillatory shear stress, preventing the induction of valve-associated genes. Disrupted transport of immune cells, driven by loss of valve integrity and TLO formation, may contribute to the pathology of Crohn's disease.

Growth inhibitory effect of selected medicinal plants from Southern Ethiopia on the mycelial phase of Histoplasma capsulatum var. farciminosum.

BACKGROUND: Epizootic lymphangitis is an infectious and chronically debilitating disease of the equines. Histoplasma capsulatum var. farciminosum, a thermally dimorphic fungi, is the causative agent for the disease. In Ethiopia, the disease significantly affects carthorses, posing threats to animal welfare, and resulting in substantial economic losses. Limited availability of widely accessible antifungals in addition to the chronic nature of the disease is the major challenge against management of epizootic lymphangitis. This study aimed to assess the in vitro efficacy of specific local medicinal plant extracts against the mycelial phase development of H. capsulatum var. farciminosum in southern Ethiopia. The leaves of Xanthium strumarium, Kanda (Family Rubiaceae), Croton macrostachyus (Bisana in Amharic), and Centella Asiatica (Echere waye as a local name in Zeyissegna) that are traditionally used for the treatment of different skin ailments were collected and extracted for the in vitro trial. RESULTS: The study revealed that methanol extracts of Xanthium strumarium, Kanda, Croton macrostachyus, and Centella Asiatica, at minimum inhibitory concentrations of 1.25 mg/ml, 2.5 mg/ml, 2.5 mg/ml, and 5 mg/ml, respectively, inhibited the growth of H. capsulatum var. farciminosum. CONCLUSION: This in vitro finding could serve as significant preliminary data in the exploration of effective alternative treatment options for epizootic lymphangitis. This study provides a crucial foundation for further research aimed at determining the chemical components and in vivo effectiveness of these plant extracts against both the mycelial and yeast forms of Histoplasma capsulatum var. farciminosum.

Thoracic lymphangitis as an immune-related adverse event: a case report.

The efficacy of immune checkpoint inhibitors (ICIs) has been widely recognized in several cancers and is now being used in the perioperative setting for lung cancer.We recently encountered an immune-related adverse event that has not been previously reported: thoracic lymphangitis, which occurred after postoperative ICI treatment for lung cancer. The patient complained of breathlessness and her condition rapidly progressed to hypoxia grade 3. Chest computed tomography revealed significant lymphostasis. With high-dose steroid treatment, the patient showed improvement.Therefore, as the frequency of neoadjuvant, adjuvant, and perioperative ICI use is expected to increase, it is crucial to understand and monitor this adverse event.

Lymphangitic Melanomatosis: Case Report of Intralymphatic Spread of Melanoma in a 66-year-old Man.

ABSTRACT: Melanoma with lymphatic invasion has been associated with increased risk of metastasis, but the mechanisms and clinical implications are poorly understood. Although current reports have documented angiotropic spread of melanoma and suggest lymphatic spread of melanoma to increase the likelihood of metastasis, to our knowledge, lymphangitic metastatic melanoma resembling cutaneous carcinomatosis or presenting with facial hyperpigmentation has not been described. In this case report, we describe extensive cutaneous intralymphatic spread of melanoma, or lymphangitic melanomatosis, producing macular skin pigmentation in a 66-year-old man.

[Recurrent Breast Cancer with Pulmonary Lymphangitis Carcinomatosis Case Responding to Trastuzumab Deruxtecan].

Pulmonary lymphangitis carcinomatosis is generally characterized by resistance to chemotherapy and is associated with a poor prognosis. Herein, we present a case of pulmonary lymphangitic carcinomatosis from recurrent breast cancer that responded well to trastuzumab deruxtecan(T-DXd). The patient was a 40-year-old woman with hormone receptor-positive, HER2-positive breast cancer. At the age of 31, she had undergone a left mastectomy with axillary lymph node dissection. She received adjuvant chemotherapy(5-fluorouracil-epirubicin-cyclophosphamide, docetaxel, and trastuzumab)followed by endocrine therapy(tamoxifen and LH-RHa). Three years after the surgery, pulmonary and bone metastases were detected and she was treated with trastuzumab, pertuzumab, and capecitabine. Liver metastases were detected, and she was treated with trastuzumab emtansine. Nine years after surgery, the patient developed dyspnea and was diagnosed with lymphangitis carcinomatosis. After initiating T-DXd, dyspnea rapidly improved, and ground glass opacity on CT scan disappeared. She responded well to the treatment, with prolonged, stable disease for 1 year and 2 months. Thus, T-DXd may be effective against pulmonary lymphangitis carcinomatosis, which is generally characterized by resistance to chemotherapy.

Comparative investigations into the growth details of Histoplasma capsulatum var farciminosum on four different agar media.

Epizootic equine lymphangitis (EEL) is a chronic fungal disease that affects equids. The causative agent is a dimorphic fungus called Histoplasma capsulatum var farciminosum. Histoplasmacapsulatum var farciminosum field strain 7 (D 2878/2023) isolated from the eye socket of an EEL Ethiopian horse was sub-cultured on four different solid media and incubated at 26°C and 37°C for 6 weeks. Details of growth morphology were recorded and shown in images during 6 weeks of incubation. Histoplasmacapsulatum var farciminosum grew best at 26°C on all four agars, but only on sheep blood agar at 37°C as small, white dry colonies.

Histoplasma capsulatum var farciminosum was isolated from the eye socket of an equine epizootic lymphangitis infected Ethiopian horse on Mycosel agar, which was sub-cultured on four different solid media at two different temperatures for 6 weeks to show its growth pattern.

Risk Factors Associated with Adverse Outcomes after Ablative Surgery for Lymphedema.

BACKGROUND: Postmastectomy breast cancer lymphedema poses an important health threat. Historically, physical therapy was the exclusive treatment option. More recently, lymphedema surgery has revolutionized care. As a first-in-kind, multicenter report, the postmastectomy breast cancer patients' risk factors associated with postlymphedema ablative surgical outcomes were documented. METHODS: Using the New York Statewide Planning and Research Cooperative System database from 2010 to 2018, multivariable models identified the postmastectomy breast cancer lymphedema surgical patients' characteristics associated with major adverse outcomes and mortality. RESULTS: Of 65,543 postmastectomy breast cancer patients, 1,052 lymphedema surgical procedures were performed including 393 (37.4%) direct excisions and 659 (63.6%) liposuctions. Direct excision and liposuction surgical patients had median ages of 58 and 52 years, respectfully (p < 0.001). Although a 30-day operative mortality was rare (0.3%, all direct excisions), major adverse outcomes occurred in 154 patients (28.5% direct excision; 6.4% liposuction; p < 0.0001). Multivariable clinical outcomes model identified that patients with higher Elixhauser's score, renal disease, emergent admissions, and direct excision surgery had higher incidences of adverse outcomes (all p < 0.01). For those patients with 30-day readmissions (n = 60), they were more likely to have undergone direct excision versus liposuction (12.5 vs. 1.7%; p < 0.0001). The important risk factors predictive of future cellulitis/lymphangitis development included diabetes mellitus, Medicaid insurance, renal disease, prior cellulitis/lymphangitis, chronic obstructive pulmonary disease (COPD), and chronic steroid use (all p < 0.01). CONCLUSION: Lymphedema surgery carries a favorable risk profile, but better understanding the "high-risk" patients is critical. As this new era of lymphedema surgery progresses, evaluating the characteristics for adverse postoperative outcomes is an important step in our evolution of knowledge.

Ultrasonographic features of intestinal lipogranulomatous lymphangitis in 10 dogs.

Intestinal lipogranulomatous lymphangitis (ILL) is a granulomatous inflammation of the lymphatic vessels of the intestinal wall and mesentery characterized by lipogranulomas. The purpose of this retrospective, multi-center, case series study is to report the ultrasonographic features of canine ILL. Ten dogs with a histologically confirmed ILL undergoing preoperative abdominal ultrasound were retrospectively included. Additional CT was available in two cases. Lesion distribution was focal in eight dogs and multifocal in two. All dogs presented with intestinal wall thickening and two had a concomitant mesenteric mass adjacent to the intestinal lesion. All lesions were in the small intestine. Ultrasonographic features were altered wall layering with predominantly muscular and to a lesser extent submucosal layer thickening. Other findings included hyperechoic nodular tissue within the muscular, serosa/subserosal, and mucosal layers, hyperechoic perilesional mesentery, enlarged submucosal blood/lymphatic vessels, mild peritoneal effusion, intestinal corrugation, and mild lymphadenomegaly. The two intestinal to mesenteric masses presented heterogeneous echostructure, predominantly hyperechoic with multiple hypo/anechoic cavitations filled with mixed fluid and fat attenuation content on CT. Histopathological findings included lymphangiectasia, granulomatous inflammation, and structured lipogranulomas affecting mainly submucosa, muscularis, and serosa. The intestinal to mesenteric cavitary masses revealed severe granulomatous peritonitis with steatonecrosis. In conclusion, ILL should be considered as a differential diagnosis for dogs with this combination of ultrasonographic features.

Nodular lymphangitis related to methicillin-resistant staphylococcus aureus infection.

Nodular lymphangitis, also known as lymphocutaneous syndrome or sporotrichoid lymphangitis, presents with inflammatory nodules along the lymphatic vessels, typically involving the upper or lower extremities. Although the most common cause of nodular lymphangitis is infection due to Sporothrix schenckii, Nocardia brasiliensis, Mycobacterium marinum, or Leishmania braziliensis, it is important for clinicians to be aware of methicillin-resistant Staphylococcus aureus as a rare cause of nodular lymphangitis and perform gram stain, bacterial culture, and antibiotic sensitivity profiles when appropriate. History of recent travel or exposures, incubation time, presence of systemic symptoms, and presence of ulceration, suppuration, or drainage can serve as diagnostic clues, but microbiological tissue cultures and histopathologic studies confirm the diagnosis. Herein, we present a case of nodular lymphangitis caused by methicillin-resistant Staphylococcus aureus (MRSA); tissue culture and antibiotic sensitivities were used to guide treatment.

Cutaneous lymphangitis carcinomatosa: a unique presentation of a rare disease.

A 75-year-old man with a three-year history of metastatic lung adenocarcinoma was diagnosed with cutaneous lymphangitic carcinomatosa of unique morphology. He was admitted to our hospital for right neck swelling, erythema, and failure to thrive. Skin examination demonstrated an indurated, thickened, firm, hyperpigmented plaque extending from the right neck and chest to the right ear, cheek, and eyelids. Skin biopsy demonstrated poorly differentiated adenocarcinoma, morphologically consistent with metastasis from the patient's known pulmonary adenocarcinoma and showed dermal invasion, perineural invasion, and involvement of dermal lymphatics. The diagnosis was an atypical presentation of cutaneous lymphangitis carcinomatosa from metastatic lung adenocarcinoma. This case presentation affirms that cutaneous lymphangitis carcinomatosa has a variety of atypical presentations, so physicians must maintain a high index of suspicion when evaluating cutaneous lesions in patients with known or suspected internal malignancy.

[A Case of Gastric Cancer with Pulmonary Carcinomatous Lymphangitis and Disseminated Carcinomatosis of the Bone Marrow Responding to S-1 plus Cisplatin Chemotherapy].

A 63-year-old man was admitted to a hospital owing to shortness of breath. He was diagnosed as having gastric cancer with pulmonary carcinomatous lymphangitis(PCL)and disseminated carcinomatosis of the bone marrow(DCBM). Regarding tumor markers, carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9)levels increased to 332 ng/ mL and 921 U/mL, respectively. Since the disease was also accompanied by disseminated intravascular coagulation(DIC), S- 1 plus cisplatin chemotherapy was started immediately(S-1 120 mg/body administered for 21 days and cisplatin 60 mg/m2 administered on day 8, 35 days for a course). Approximately 2 weeks after the initiation of chemotherapy, the patient's respiratory symptoms improved, and he recovered from DIC. After 2 chemotherapy courses, tumor marker levels decreased (CEA 9.3 ng/mL and CA19-9 314 U/mL), and the patient continued to receive chemotherapy without the deterioration of his physical condition for 5 months. However, he experienced fatigue after 4 courses, because of the progression of gastric cancer. Although the regimen was changed to ramucirumab plus paclitaxel chemotherapy, the patient died 8 months after the initiation of chemotherapy. An accumulation of cases is needed to establish treatment strategies for gastric cancer with PCL and/or DCBM.

Lymphangitis Carcinomatosa in Neck Soft Tissue: Computed Tomography Findings With Emphasis on Differentiation From Cellulitis.

OBJECTIVE: Lymphangitis carcinomatosa (LC) is a rare form of metastasis. The purposes of this study were to evaluate computed tomography (CT) findings associated with LC in neck soft tissue and to determine those that were useful in distinguishing LC from cellulitis. METHODS: Contrast-enhanced CT images of 26 patients with pathologically confirmed LC (n = 5) and clinically proven cellulitis (n = 21) were reviewed retrospectively. The following CT findings were evaluated and compared between the 2 groups: subcutaneous fat infiltration, enlargement of muscle, thick irregular enhancement of the superficial cervical fascia, grouping of micronodules, focal intramuscular enhancement, localized fluid collection, and nodular skin thickening. RESULTS: Thick irregular enhancement of the superficial cervical fascia (80.0% vs 0%, P < 0.0005), grouping of micronodules (60.0% vs 0%, P < 0.005), and focal intramuscular enhancement (60.0% vs 4.8%, P < 0.05) were significantly more frequent in LC than in cellulitis. Other findings did not show statistical significance between both groups. CONCLUSIONS: When soft tissue swelling is present in the neck with either thick irregular enhancement of the superficial cervical fascia, grouping of micronodules, or focal intramuscular enhancement, the possibility of LC should be considered especially in patients with underlying malignancy.

Objective Thoracoscopic Criteria in Differentiation between Benign and Malignant Pleural Effusions.

BACKGROUND: Thoracoscopy is the "gold standard" diagnostic modality for investigation of suspected pleural malignancy. It is postulated that meticulous assessment of the pleural cavity may be adequate to indicate malignancy through the macroscopic findings of nodules, pleural thickening, and lymphangitis. We attempted to critically assess this practice, by precisely defining objective macroscopic criteria which might differentiate benign from malignant pleural diseases according to intrapleural pattern and anatomical location, and thereby to explore the predilection of abnormalities to specific sites on pleural surfaces. METHODS: A structured review of recorded video footage from medical thoracoscopy procedures in 96 patients was conducted by 2 independent assessors. Abnormalities were scored on agreed, objective criteria for the presence of nodules, lymphangitis and inflammation on each of the costoparietal, visceral and diaphragmatic surfaces. The costoparietal pleura was divided into 6 levels (apical, middle, and inferior surfaces of the lateral and posterior parietal pleura). The anterior surface of the costoparietal pleura was excluded from analysis after interim review as this surface was rarely seen. RESULTS: In the benign group, inflammation was the predominant finding in 65% (n = 33; costoparietal), 44% (n = 21; visceral), and 42% (n = 15; diaphragmatic). Nodules were detected in 24% (n = 12; costoparietal), 8% (n = 4; visceral), and 8% (n = 3; diaphragmatic). The most affected surfaces with inflammation were the middle lateral (60%) and the inferior lateral (57.8%) parts of the costoparietal pleura. In the malignant group, nodules were the predominant finding according to surface in 73% (n = 33; costoparietal), 32% (n = 13; visceral) and 48% (n = 17; diaphragmatic). Inflammation was detected in 44% (n = 20; costoparietal), 25% (n = 10; visceral), and 29% (n = 10; diaphragmatic). The most affected surfaces with nodules were the middle lateral (67.4%) and inferior lateral (66.7%) costoparietal pleural surfaces. CONCLUSION: This is the first detailed, anatomical description of abnormalities in the pleural space during thoracoscopy. While nodules were the predominant pattern in malignant pleural effusion, they were detected in 24% of benign diagnoses. Detection of nodules in >1 area of the costoparietal pleura was in favor of a malignant diagnosis. Inflammation was the predominant pattern in benign pleural effusion. Our results suggest that macroscopic nodules in malignant diagnoses have a predilection for the middle and inferior surfaces of the lateral costoparietal pleura.

[Duodenal lymphangitis carcinomatosa: a rare endoscopic finding]. / Duodenale Lymphangiosis carcinomatosa: ein seltener endoskopischer Befund.

We herein report a case of a 67-year-old male with a rare endoscopic finding in the duodenum. Upon gastroscopic inspection, the duodenal mucosa showed lymphectasia. The histology of these lesions surprisingly described lymphangitis carcinomatosa of the duodenum, which has only been described in a few cases so far. As the prognosis of patients with this condition is poor, endoscopists should have a high degree of awareness of this finding.

Long-term patency of multiple lymphatic-venous anastomoses in cancer-related lymphedema: A single center observational study.

OBJECTIVES: Lymphedema is always initially treated by combined decongestive physiotherapy (CDP). Those cases, refractory to CDP, may be managed by surgical therapy. One of the most used microsurgical procedures is represented by the technique of lymphatic-venous anastomosis (LVA). But very few papers report long term results of LVA. The aim of this study is to assess the long-term patency of multiple lymphatic-venous anastomosis (MLVA) for the treatment of secondary lymphedemas. METHODS: From January 2014 to December 2014, 101 patients (mean age: 56.94 ± 8.98 years; female/male: 86/15) affected by secondary cancer-related lymphedema (38 lower and 63 upper limbs) were treated by MLVA. All lymphedemas had previously been treated by conservative therapy without sustained results. Many patients (78%) had 1-3 episodes of acute lymphangitis/year. Lymphoscintigraphy, venous duplex-ultrasonography, and abdominal or axillary ultrasound investigation were performed preoperatively. MLVA patency was assessed by the lymphatic transport index (LyTI) and lymphoscintigraphic pattern. RESULTS: At 1 year after surgery, excess volume reduction was 75%-90% in the early stage II secondary lymphedemas, and 60%-75% in the late stage II. The decrease in volume maintained stability in the 5-years follow-up period. Two more advanced lower and one upper limb lymphedemas had 45%-60% reduction. LyTI showed a significant decrease between the preoperative mean value (31.7 ± 9.43) and after 18 months from surgery (11.2 ± 1.91) (p < .001). MLVA patency was shown in 98 (97%) patients. No patients had evidence of postoperative lymphangitis. CONCLUSIONS: This study demonstrated the long-term patency of MLVA in the treatment of cancer-related lymphedemas.

A TNF-p100 pathway subverts noncanonical NF-κB signaling in inflamed secondary lymphoid organs.

Lymphotoxin-beta receptor (LTßR) present on stromal cells engages the noncanonical NF-κB pathway to mediate RelB-dependent expressions of homeostatic chemokines, which direct steady-state ingress of naïve lymphocytes to secondary lymphoid organs (SLOs). In this pathway, NIK promotes partial proteolysis of p100 into p52 that induces nuclear translocation of the RelB NF-κB heterodimers. Microbial infections often deplete homeostatic chemokines; it is thought that infection-inflicted destruction of stromal cells results in the downregulation of these chemokines. Whether inflammation per se also regulates these processes remains unclear. We show that TNF accumulated upon non-infectious immunization of mice similarly downregulates the expressions of these chemokines and consequently diminishes the ingress of naïve lymphocytes in inflamed SLOs. Mechanistically, TNF inactivated NIK in LTßR-stimulated cells and induced the synthesis of Nfkb2 mRNA encoding p100; these together potently accumulated unprocessed p100, which attenuated the RelB activity as inhibitory IκBδ. Finally, a lack of p100 alleviated these TNF-mediated inhibitions in inflamed SLOs of immunized Nfkb2-/- mice. In sum, we reveal that an inhibitory TNF-p100 pathway modulates the adaptive compartment during immune responses.

Is lymphangitic streaking associated with different pathogens?

OBJECTIVES: Little is known regarding the differences in microbiology associated with cellulitis or abscess with or without lymphangitic streaking. The objective of our study is to assess whether there are differences in the pathogens identified from wound cultures of patients with paronychia with and without associated lymphangitis. METHODS: Retrospective cross-sectional study at a tertiary pediatric emergency department over 25 years. We opted to assess patients with paronychia of the finger, assuming that these cases will have a greater variety of causative pathogens compared to other cases of cellulitis and soft tissue abscess that are associated with nail biting. Case identification was conducted using a computerized text-screening search that was refined by manual chart review. We included patients from 1 month to 20 years of age who underwent an incision and drainage (I&D) of a paronychia and had a culture obtained. The presence or absence of lymphangitis was determined from the clinical narrative in the medical record. We excluded patients treated with antibiotics prior to I&D as well as immune-compromised patients. We used descriptive statistics for prevalence and χ2 tests for categorical variables. RESULTS: Two hundred sixty-six patients met inclusion criteria. The median age was 9.7 years [IQR 4.7, 15.4] and 45.1% were female. Twenty-two patients (8.3%) had lymphangitic streaking associated with their paronychia. Patients with lymphangitis streaking were similar to those without lymphangitis in terms of age and sex (p = 0.52 and p = 0.82, respectively). Overall, the predominant bacteria was MSSA (40%) followed by MRSA (26%). No significant differences were found between the pathogens in the 22 patients with associated lymphangitis compared to the 244 patients without. CONCLUSION: Staphylococcus aureus represent the majority of pathogens in paronychia, although streptococcal species and gram-negative bacteria were also common. Among patients with paronychia of the finger, there seems to be no association between pathogen type and presence of lymphangitic streaking.

Nocardia takedensis: a newly recognized pathogen responsible for skin and soft tissue infections.

Nocardia takedensis was first isolated in 2005, from soil in Japan. We report here two cases of lymphangitis in France (2012-2017) caused by N. takedensis both occurring after skin injury while gardening, which enabled its inoculation. The two patients were immunocompromised and successfully treated by an antimicrobial agent active on the isolated strain, trimethoprim-sulfamethoxazole and amoxicillin-clavulanic acid for patient one and patient two, respectively. Our study along with previous ones supports the idea of a newly recognized cutaneous opportunistic pathogen and reinforces the recommendation of using gloves during soil exposure for immunocompromised patients. Lastly, according to data found in the literature, we would recommend trimethoprim-sulfamethoxazole as an efficient empirical antibiotic therapy in case of cutaneous infection caused by N. takedensis.

Epidemiology of epizootic lymphangitis of carthorses in northern Ethiopia using conventional diagnostic methods and nested polymerase chain reaction.

BACKGROUND: Epizootic lymphangitis (EL), caused by Histoplasma capsulatum variety farciminosum (HCF) is a contagious, chronic disease of equines, characterized by development of nodular lesions in the lymph nodes, lymphatic vessels and skin. It is one of the most important diseases of equines in Ethiopia, causing significant economic loss, particularly in the livelihood of carthorse owners. To date there is neither effective diagnostic nor control measure implemented in the country. Furthermore, there is a shortage of data on the epidemiology of the disease in different regions of this country. The aim of this study was to investigate epidemiology of EL in northern Ethiopia, using the conventional methods as well as nested polymerase chain reaction (PCR). RESULTS: The presence of HCF genetic material was confirmed in 44% (84/191) of the carthorses. Subclinical infection was observed in 18.2% (22/121) of the apparently healthy carthorses. Considering the nested PCR as a gold standard, sensitivity and specificity of clinical examination were 74% and 92.5%, respectively, while the area under the ROC curve (AUR) was 0.83 (95% confidence interval, 0.77, 0.896). Moreover, a moderate (k = 0.675) agreement observed between the nested PCR and clinical examination. CONCLUSIONS: This study demonstrated widespread occurrence of EL in northern Ethiopia, and the advantage of the nested PCR in detecting infection of HCF, even before the clinical symptoms became apparent.