Dilated Lymphatic Channels Research Articles

Atypical presentation of a lymphangioma as a conjunctival horn.

Conjunctival lymphangiomas are rare hamartomas of lymphatic origin that are usually located in the bulbar conjunctiva. They commonly present either as focal or diffuse bulbar chemosis or as dilatation of lymphatic vessels that resembles an isolated cyst or a group of cysts. There can be bleeding inside the lymphangioma resulting in "chocolate cysts".1 We report the unusual case of a conjunctival lymphangioma on a 36 year-old male that presented as a large horn-like protruding structure. The lesion was surgically removed with simple excision associated with cryotherapy to the lesion's borders, as malignancy could not be ruled out preoperatively. Histopathological examination revealed a lymphangioma composed of an ill-defined proliferation of dilated lymphatic channels in the lamina propria, underlying conjunctival epithelium with squamous metaplasia, acanthosis and hyperkeratosis. One year postoperatively, the patient remains asymptomatic and without recurrence of the lesion.

Acquired Cutaneous Lymphangiectasia of Vulva: A Novel Dermoscope Finding.

A 61-year-old woman presented with a 1-year history of multiple, oozy, raised pruritic lesions over the genitalia. Four years back, she had undergone radical hysterectomy followed by loco-regional radiotherapy for her stage IIA carcinoma cervix. On physical examination, she had multiple, grouped, translucent, thin-walled vesicles resembling “frogspawn” on the bilateral labia majora [Figure 1]. Histopathological examination showed a hyperkeratotic epidermis with multiple dilated lymphatic channels in the superficial and deep dermis. Dermoscopy (Dermlite 4) revealed clustered, translucent, reddish-white lacunae surrounded by whitish septa. Few lacunae showed radially arranged, hairpin-like vessels [Figure 2]. The features were consistent with acquired cutaneous lymphangiectasia of vulva (ACLV). Radiofrequency ablation of the lesions was performed and she was under regular follow-up.Figure 1: Multiple, grouped, translucent to flesh-colored, fluid-filled vesicles - ”frogspawn appearance” on labia majoraFigure 2: Dermoscopy (Dermlite 4: Polarized view, 10× magnification) showing clustered, translucent, reddish-white lacunae surrounded by whitish septa (yellow circle). Few lacunae showed radially arranged hairpin-like vessels (black circles)ACLV is a rare entity, which occurs secondary to conditions like trauma, surgery, keloids, radiation, scleroderma, pregnancy, malignancies, Crohn’s disease, or infections like erysipelas, tuberculosis, filariasis, and lymphogranuloma venereum. These conditions cause destruction of lymph nodes and impair lymphatic flow thereby resulting in the accumulation of lymph in dermal lymphatics producing vesicles.[1] The differential diagnosis includes lymphangioma circumscriptum, syringoma, condyloma, herpes, warts, molluscum contagiosum, and benign hemangioendothelioma.[12] Errichetti et al.[3] in their dermoscopy of ACLV reported a vascular pattern with well-demarcated, round to oval red lacunae surrounded by white areas/lines with several punctiform and a few irregular vessels. In addition, we have observed radially arranged hairpin-like vessels in our case. In dermoscopy, similar hairpin-like vessels are found in seborrheic keratosis, keratoacanthoma, squamous cell carcinoma, amelanotic melanoma, superficial basal cell carcinoma (BCC), nodular BCC, eccrine poroma, porocarcinoma, and pilomatrixoma.[4] We report this case for the novel dermoscopic finding. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Endoscopic resection of upper gastrointestinal lymphangioma: A single-center experience.

Lymphagioma, which in most cases as benign tumors, occurs in head, neck, axilla, and mediastinum. Lymphangioma is exceedingly rare in the upper gastrointestinal tract including esophagus, stomach, and duodenum. However, the clinical characteristics, natural history, and recurrence rate after endoscopic resection remain unclear. This study aims to evaluate the characteristic findings and assess the efficacy of endoscopic techniques in the management of this disease. In this systematic retrospective analysis, we evaluated all 24 cases of upper gastrointestinal lymphangioma resected by endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) and diagnosed by histopathology at our hospital from January 2012 to May 2021. We analyzed the results of endoscopy, endoscopic ultrasonography (EUS), CT, histologic examination, and follow-up assessments. 9 male and 15 female patients with esophageal lymphangioma were enrolled in this study, with a mean age of 54.17 ± 11.60 years (range 30-71 years). The lesions' size varied from 2.20 to 40.10 mm, with the median size of 7.83 mm. All patients were evaluated preoperatively, whose endoscopic appearance typically appears as dilated lymphatic channels beneath the surface epithelium of the protrude mucosal or sub-mucosal lesion. Endoscopic ultrasonography revealed the presence of a honeycomb-like or grid-like mass with a heterogeneous echo pattern, and a clear boundary between the lesion and the muscularis propria layer may be helpful for the primary diagnosis of this disease. 22 patients underwent EMR and 2 patient were treated with ESD. Histologic examination revealed that the lesions contained many dilated lymphatic vessels, which confirmed the initial diagnosis of lymphangioma in all patients. No major adverse events were found during the operation or a median follow-up of 43 months (range 13-92). Endoscopic ultrasonography has important clinical value for the primary diagnosis of lymphangioma in the upper gastrointestinal tract. This study also suggests that endoscopic resection should be considered as a more minimally invasive, safe, feasible, and effective therapeutic option comparing to laparoscopic surgery.

S1994 Cecal Lymphangioma During Routine Colonoscopy

Introduction: Abdominal lymphangioma is a rare finding. Most of them arise from the mesentery or omentum, and those arising from the GI tract is extremely rare. Lymphangioma involving the colon is usually asymptomatic and can be encountered during screening colonoscopy. It is characterized by a soft, cystic appearing lesion that contains dilated lymphatic channels. Cecal lesions should be differentiated from appendiceal neoplasms including mucocele and carcinoid tumors. Case Description/Methods: A 61-year-old male underwent a screening colonoscopy which revealed a soft cystic lesion in the cecum measuring about 20 mm wide, with a positive cushion sign. Appendiceal orifice and the ileocecal valve appeared normal. CT of the abdomen showed a low-density cystic lesion arising from the wall of the cecum and separate from the appendix. Endoscopic ultrasound (EUS) exam using a mini ultrasound probe revealed a cystic anechoic subepithelial lesion measuring (18 x 17 mm) with septations arising from the submucosa (Figure). Discussion: Lymphangioma of the colon is a rare asymptomatic finding often encountered during screening colonoscopy. It is characterized by a soft, cystic appearing lesion that contains dilated lymphatic channels. It is often solitary and is usually benign in nature. Cecal lesions, especially if in proximity to the appendiceal orifice should be differentiated from appendiceal neoplasms including mucocele and carcinoid tumors. Lymphangioma may be difficult to be differentiated from a lipoma on endoscopic appearance. Signal characteristics on CT imaging differ between the 2; Lipomas have characteristics similar to subcutaneous fat and usually have Hounsfield unit measurements between -65 and -120; Lymphangiomas on the other hand are cystic appearing with Hounsefield units corresponding to the fluid density and the average Hounsefield unit of the lesion in our patient was 17. Similarly, endosonographic features vary between the 2. Lipomas are hyperechoic lesions arising from the submucosa, whereas lymphangiomas are anechoic. Endoscopic appearance of a cystic lesion often with a bluish hue and a positive cushion/ pillow sign and ultrasonographic features (anechoic subepithelial lesion often with septations and without solid component) aid towards the diagnosis of lymphangioma without the need for invasive tissue diagnosis. Rare cases of intussusception from large cecal lymphangioma have been reported. Given the benignity, surgical intervention is not needed in asymptomatic patients.Figure 1.: positive cushion sign.

Vulval Lymphangiectasia Post-radiotherapy in Cervical Cancer

Cutaneous lymphangiectasia is a benign cutaneous disorder of dilatation of the dermal and subcutaneous lymphatic channels, which occurs rarely on the vulva. It can be congenital or acquired developing secondary to tuberculosis, surgery, and radiotherapy. We report the case of a 58-year-old female patient who gives a history of cervical cancer, for which she underwent hysterectomy and postsurgery radiotherapy 3 years back, now presenting with multiple lumps over the vulva, which discharged clear fluid for 1 year. Acquired vulval lymphangiectasia develops 7–15 years postradiotherapy or surgery commonly, while in our case, it developed earlier. On local examination, there were multiple shiny translucent and hyperpigmented “frog-spawn like” vesicles and papules present over the lower midabdomen, mons pubis, and labia majora. Diagnosis of vulval lymphangiectasia was made on the clinical findings and biopsy. Biopsy revealed dilated lymphatic channels in the superficial and deep dermis. CO2 laser treatment was done for the patient.

Primary Intestinal Lymphangiectasia in a Middle-Aged Female.

Primary intestinal lymphangiectasia (PIL) is a rare disorder caused by impaired intestinal lymphatic drainage due to congenital lymphatic hypoplasia. It was first described by Waldman et al. in 1961,[1] about 205 cases have been reported.[2] The disease usually manifests before 3 years of age, and only occasionally diagnosed in adulthood. Here, we report a case of a middle-aged female who presented with chronic diarrhea and was finally diagnosed as a case of PIL. A 49-year-old female presented to the Outpatient Department of our hospital with complaints of diarrhea for 2 years. The patient reported an occurrence of diarrhea four to five times daily, which was semisolid to watery in consistency with absence of blood, mucus, or oil. The diarrhea was also not associated with tenesmus, urgency, or pain in the abdomen. On examination, her body mass index was 18 kg/m2 and there was presence of bilateral pitting edema in the lower limbs. Routine laboratory investigation revealed hemoglobin of 9 gm/dl, total leukocyte count of 4100/mm3 with 14% of lymphocytes, platelet count of 1.6 lakh/mm3 and hypoproteinemia (serum protein, 3.90 gm/dl; serum albumin, 2.10 gm/dl; serum globulin, 1.8 gm/dl). She was non-reactive for HIV and hepatitis B. Stool routine and microscopic examination was negative on three occasions and culture was negative. Upper gastrointestinal endoscopy revealed multiple scattered whitish spots in the second part of the duodenum [Figure 1]. Multiple biopsies from it revealed dilated lymphatic channels in lamina propria, muscularis mucosae and submucosa [Figure 2]. Therefore, a diagnosis of intestinal lymphangiectasia (IL) was made and further work up was done to rule out secondary causes. Her colonoscopy with terminal ileoscopy, contrast-enhanced computed tomography of chest and abdomen, echocardiography, autoimmune profile, immunoglobulin levels and hormonal profile were all normal except for reduced immunoglobulin levels. Accordingly, a final diagnosis of PIL was made and the patient was started on a low-fat, high-protein diet with medium-chain triglyceride (MCT) supplementation. Subsequently, her condition improved, and the diarrhea stopped after 1 month. The upper gastrointestinal endoscopy was repeated after 6 months, and the findings were normal with no whitish spots in the duodenum [Figure 3].Figure 1: Upper gastrointestinal endoscopy showing whitish spots in the second part of duodenumFigure 2: Duodenal biopsy showing dilated lacteals in mucosa and submucosaFigure 3: Normal upper gastrointestinal endoscopy after 6 months of dietary modificationPIL is a congenital malformation that presents with chronic diarrhea and malabsorption and is diagnosed after ruling out secondary causes. Its late onset can be explained by the patchy involvement of the small bowel. Secondary intestinal lymphangiectasia can occur due to various causes such as constrictive pericarditis, intestinal lymphoma, intestinal tuberculosis, sarcoidosis, scleroderma, Whipple's disease, Crohn's disease, autoimmune polyglandular syndrome and radiation or chemotherapy induced retroperitoneal fibrosis.[3] Intestinal lymphangiectasia in adults has few or no features of malabsorption, as in our case. Its diagnosis is done by specific endoscopic features and corresponding histopathological findings. Endoscopic features of intestinal lymphangiectasia are scattered white punctate snowflake lesions in small intestine due to dilated lacteals that cannot be washed away. Upper gastrointestinal endoscopy can diagnose 86% of intestinal lymphangiectasia cases.[4] Histopathology of small bowel will show characteristic dilated lacteals in the mucosa and submucosa. The cornerstone of its treatment is diet modification. Diet should be low in fat with substitution of long chain fatty acid with MCT, as it directly enters the portal venous system bypassing the intestinal lacteal system, thereby preventing lacteal engorgement and rupture.[5] Most of the patient respond with this treatment in few weeks with reversal of clinical and biochemical signs. In conclusion, PIL is a rare cause of chronic diarrhea, especially in adulthood, that requires meticulous examination of duodenum, as early diagnosis and treatment can reduce the morbidity and mortality. Declaration of patient consent The authors certify that they have obtained all appropriate consent forms from the patient. The patient has given her consent for images and other clinical information to be reported in the Journal. The patient understands that her name and initials will not be published, and due efforts will be made to conceal the identity. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Lymphatic Endothelial Cell Defects in Congenital Cardiac Patients With Postoperative Chylothorax

Objectives:Chylothorax following cardiac surgery for congenital cardiac anomalies is a complication associated with severe morbidities and mortality. We hypothesize that there are intrinsic defects in the lymphatics of congenital cardiac patients.Methods:Postsurgical chylothorax lymphatic endothelial cells (pcLECs) (n = 10) were isolated from the chylous fluid from congenital cardiac defect patients, and characterized by fluorescent-activated cell sorting, immunofluorescent staining, and quantitative RT-PCR. Results were compared to normal human dermal lymphatic endothelial cells (HdLECs). pcLECs (n = 3) and HdLECs were xenografted into immunocompromised mice. Implants and postoperative chylothorax patient’s pulmonary tissues were characterized by immunostaining for lymphatic endothelial proteins.Results:pcLECs expressed endothelial markers VECADHERIN, CD31, VEGFR2, lymphatic endothelial markers PROX1, podoplanin, VEGFR3, and progenitor endothelial markers CD90 and CD146. However, pcLECs had key differences relative to HdLECs, including altered expression and mislocalization of junctional proteins (VECADHERIN and CD31), and essential endothelial proteins, VEGFR2, VEGFR3, and PROX1. When xenografted in mice, pcLECs formed dilated lymphatic channels with poor cell–cell association. Similar to congenital lymphatic anomalies, the pulmonary lymphatics were dilated in a patient who developed postoperative chylothorax after cardiac surgery.Conclusions:Recent studies have shown that some postoperative chylothoraces in congenital cardiac anomalies are associated with anatomical lymphatic defects. We found that pcLECs have defects in expression and localization of proteins necessary to maintain lymphatic specification and function. This pcLEC phenotype is similar to that observed in lymphatic endothelial cells from congenital lymphatic anomalies. Co-existence of lymphatic anomalies should be considered as a feature of congenital cardiac anomalies.

Lymphangioma of popliteal fossa masquerading as Baker\u2019s cyst

BackgroundLymphatic malformations are the second most common vascular malformations after venous malformations. These slow-flow lesions occur most often in the paediatric population and seldom in the extremities. We report a case of lymphangioma at the popliteal fossa in an adult who underwent complete surgical resection.Case presentationA 30-year-old male presented to the department of orthopaedics with a swelling in the right calf region. Clinically, it was suspected to be a Baker’s cyst. Ultrasound showed a multiloculated anechoic cystic lesion in the inferior aspect of popliteal fossa along the intermuscular plane with multiple internal septations. Infected Baker’s cyst was considered, and MRI was suggested for further evaluation. On MRI, the lesion measured 7.2 × 4.6 × 5.8 cm, appeared as a low signal on T1 and high signal on STIR and T2, with multiple internal septations and was situated in the inferior aspect of the right popliteal fossa along the intermuscular plane between the lateral head of gastrocnemius and soleus muscles. No obvious synovial extension. A post-contrast study showed minimal peripheral and septal enhancement. Neither internal enhancing solid components nor significant internal derangement of the knee was observed. Diagnosis of lymphangioma was considered based on the imaging features and ruling out the common differentials for cystic lesions around the knee. Wide local excision was performed. Histopathological evaluation showed multiple irregularly dilated lymphatic channels lined by flatted epithelium. The lymphatic channels were seen to be surrounded by thick fibro collagenous cyst wall with scattered congested blood vessels, skeletal muscle fibre and chronic inflammatory cells.ConclusionLymphangioma must be included in the differential diagnosis of any cystic lesion if the lesion appears multiseptated and/or infiltrative. At the popliteal fossa, it presents as a multiseptated cyst with no synovial continuity or internal derangement of the knee.

Angiosarcoma arising in massive localized lymphedema

We report a case of a 70-year-old woman with a BMI of 58 who developed cellulitis refractory to treatment, within an area of massive localized lymphedema. Biopsy showed angiosarcoma. MRI showed multiple lobulated, low T1, high T2 masses within a background of prominent soft tissue septal stranding, dilated lymphatic channels, and skin thickening. CT also showed the mass well, within the background lymphedema. Massive localized lymphedema is increasing in prevalence due to the worsening obesity epidemic. Radiologists should be aware that the presence of a nodule within an area of massive localized lymphedema is suspicious for sarcoma.

Left Hemifacial Lymphatic Malformation in a Nine-Year-Old Boy

Left Hemifacial Lymphatic Malformation in a Nine-Year-Old Boy

3211 An Incidental Duodenal Lymphangioma Presenting as Diarrhea

Introduction: The small bowel is a rare site for neoplasia and only account for over 3% of the cases in the digestive tract. Lymphangiomas are benign tumors formed by dilated lymphatic channels that occur more commonly in the neck and axillary regions. Duodenal lymphangiomas are extremely rare in the adult population. It s thought to be a benign congenital malformation of the lymphatic vasculature that is able to grow to form a mass lesion. Their clinical presentation ranges from asymptomatic to obscure bleeding, small bowel obstruction, intussusception or even volvulus. We present a case of a duodenal lymphangioma presenting with chronic abdominal pain and diarrhea. CASE DESCRIPTION/METHODS: A 37-year-old male with no significant past medical history presented with chronic diarrhea, constipation and abdominal discomfort for 3 years. Physical examination and laboratory data were in the normal limits. Remainder of his infectious and inflammatory workup for diarrhea was negative. He underwent endoscopy which revealed a 1-cm polypoid submucosal lesion in the post-bulbar area. Multiple deep bites-on-bite biopsies were obtained from the lesion. Histological examination showed dilated lymphatics with reactive epithelial changes, consistent with Lymphangioma. During the follow up visit the patient referred improvement of the presenting symptoms. DISCUSSION: Lymphangiomas of the duodenum are a very rare lymphatic system tumor. The clinical presentations are usually variable and nonspecific and may mimic a variety of vague abdominal symptoms like abdominal discomfort, diarrhea, anorexia, nausea, and vomiting. These lesions typically exist as small incidental polyps; however, some of these tumors present as mass lesions capable of causing bowel obstruction, abdominal pain, and gastrointestinal bleeding. By endoscopic examination, they usually appear as a sessile or semi-pedunculated mass with smooth surface mucosa with lymphatic cystic dilatation with a whitish granular appearance. These benign tumors require treatment if they are accompanied by symptoms and complications such as infection, obstruction and hemorrhage. Endoscopic unroofing or polypectomy has become the treatment of choice for small to intermediate lymphangiomas. Physicians must thus be cognizant of the differentials for small bowel nodules in order to avoid unnecessary surgical interventions.

1693 Jejunal Lymphangioma: An Unusual Etiology for Iron Deficiency Anemia

INTRODUCTION: Lymphangiomas are benign tumors characterized by cystic dilation of lymphatic vessels, and can arise from any location throughout the lymphatic system. Small bowel lymphangiomas are rare, and are primarily described in children. When found in adults, these lesions are typically an incidental finding. Pathologic small bowel lymphangiomas are particularly unusual, and have been reported as a rare etiology of massive gastrointestinal bleeding and chronic anemia. CASE DESCRIPTION/METHODS: A 65yo African American man with a history of prostate cancer, coronary artery disease, hypertension, hyperlipidemia, and peripheral artery disease was hospitalized for a 6 month history of symptomatic anemia, without signs of overt gastrointestinal blood loss. Vital signs were stable upon presentation, and initial labs were significant for a hemoglobin 8.7, mean corpuscular volume 94, ferritin 28, and iron saturation of 3%. An esophagogastroduodenoscopy was performed which was significant for mild gastropathy, and a colonoscopy that showed mild diverticulosis, a 3 mm polyp and small internal hemorrhoids, without stigmata of recent bleeding. Iron therapy was initiated, and the patient was referred to the outpatient gastroenterology clinic for further workup. The patient next underwent capsule endoscopy which showed a friable small bowel mass, with evidence of active bleeding. A single balloon enteroscopy was then performed, which revealed a 4 cm circumferential, friable, granular mass in the mid-jejunum which was biopsied and tattooed with India Ink. Biopsies of the mass revealed benign small intestinal mucosa with prominent lymphangiectasia. The patient was then referred to surgical oncology and underwent a laparoscopic assisted enteroscopy which again demonstrated the previously seen lesion occupying 75% of the small bowel lumen. The lesion was further evaluated with endomicroscopy which revealed multiple dilated blood vessels and lymphatic channels, in a background of inflammation. The cells appeared organized and without atypical features. A small bowel resection was performed, and the surgical pathology revealed a benign lymphatic malformation involving the mucosa and submucosa consistent with a lymphangioma. No invasive features or malignant cells were identified. DISCUSSION: Small bowel lymphangiomas are a rare finding, and primarily found within the duodenum. We report an unusual case of a large jejunal lymphangioma presenting as iron deficiency anemia, which completely resolved after resection of the mass. Watch the video: http://bit.ly/2LvNhpc.

Successful Immunoglobulin Replacement with Subcutaneous Immunoglobulin Therapy in a Patient with Primary Intestinal Lymphangiectasia

Primary intestinal lymphangiectasia is a rare disorder which characterized by impaired small intestinal lymph drainage. There is loss of proteins from dilated lymphatic channels located in the mucosa, submucosa or subserosa which is results with loss of gammaglobulins and lymphocytes, leading to impaired humoral and cellular immunity. Herein, we present a 61-year-old patient with immunodeficiency secondary to Primary intestinal lymphangiectasia (PIL), in whom we could attain effective and stable IgG levels only by subcutaneous IgG replacement rather than intravenous IgG. Our experience suggests that Subcutaneous Immunoglobulin (SCIG) replacement resulted in more stable levels of IgG in the presented patient with PIL. We concluded that SCIG should be the preferred route of immunoglobulin replacement therapy in secondary hypogammaglobulinemia due to protein losing enteropathy, especially in PIL.

Acquired Cutaneous Lymphangiectasia Secondary to Cervical Cancer Treatment

To the Editor: A 78-year-old female patient presented with a 10-year history of pedunculated nodules on her vulvar area. She remembered that the nodules had increased both in number and size over the past 10 years. The patient did not complain of any subjective symptoms, such as itching or pain. Her history included total hysterectomy and radiation therapy for cervical cancer 35 years previously, and transurethral resection of bladder tumor for bladder cancer 2 years ago with no other risk factors for lymphedema reported. Physical examination revealed multiple pinkish pedunculated translucent nodules on the labia majora (Fig. 1). Localized edema on the vulvar area was seen. A biopsy specimen was obtained through harvesting a whole nodule with a punch. The biopsy demonstrated ectatic channels in the superficial and deep dermis (Figs. 2A, B). The spaces between collagen bundles were widened, reflecting an edematous condition. No occlusive lesions or related vascular components were identified. The channel was diffusely labeled with D2–40 (Fig. 2C). A diagnosis of acquired cutaneous lymphangiectasia (ACL) was made. The patient refused treatment after realizing the benign nature of the skin lesion.FIGURE 1.: Edematous appearance of vulvar area with overlying multiple vesiculonodular lesions.FIGURE 2.: Low power (A, hematoxylin–eosin, ×40) and high power (B, hematoxylin–eosin, ×100) histologic features show dilated lymphatic channels in the papillary dermis with hyperkeratotic epidermis. No atypical cells are observed. Endothelial cell linings of ectatic channels show positive reaction to D2–40 stain (C, D2–40, ×100).Lymphedema manifests as a result of ineffective lymphatic drainage due to architectural disruption with resultant increased hydrostatic pressure.1 Common causes of acquired lymphatic compromise are surgery and radiation therapy for the treatment of malignancy. Other predisposing factors are recurrent cellulitis, Crohn disease, and urogenital tuberculosis.2 A key histologic finding for lymphedema is edematous widening of intercollagenous spaces in the papillary dermis.3 In a similar way, ACL represents acquired dilatation of lymphatic channels secondary to external causes, but it results from a more chronic process.4–6 Clinically, ACL consists of clustered translucent vesicles and nodules ranging from colorless to purple due to varying red blood cell content.7 At the time of the very first development, the new lesion appears rather vesicular while it gradually becomes nodular as a result of tissue reorganization. Histologically, ACL shows ectatic lymphatic vessels lined by normal endothelial cells.5 The overlying epidermis may show hyperkeratosis, acanthosis, and the effacement of rete ridges. The pathologic findings in this case were consistent with these features of both lymphedema and lymphangiectasia. Differential diagnosis of this unusual manifestation must include more common conditions such as genital warts, condyloma accuminatum, and molluscum contagiosum. Reported treatment options for ACL in the literature are surgical excision, laser vaporization, cryotherapy, sclerotherapy, and electrodessication. Because ACL is infamous for its high recurrence rate when deeper lymphatic abnormalities are not sufficiently destroyed, radical excision is often favored. Hamida et al,2 suggested CO2 laser ablation as a conservative alternative to surgical intervention because of high patient tolerance and good cosmetic results.

Gene Expression Differences in Pediatric Lymphatic Malformations: Size Really Matters.

Lymphatic malformations (LMs) are congenital vascular anomalies characterized by dilated and cystic lymphatic channels. They are subdivided into macrocystic and microcystic lesions based upon the predominant size of the cysts involved. However, significant differences in clinical characteristics, treatment outcomes, and prognosis between macrocytic and microcytic disease suggest variation in underlying biologic and genetic influences. Indirect differential expression analysis revealed that 426 genes are significantly different (p < 0.01) in a small sample of LM subtypes. Functional analyses on the differentially expressed gene sets showed that microcystic LM gene expression favors a prooncogenic profile with upregulation of MYC target genes and cell cycle proteins, whereas macrocystic expression demonstrates hypoxic events that lead to angiogenesis and cell proliferation. Therefore, microcystic and macrocystic LMs, although histologically and physiologically similar, may occur under the influence of vastly different biological pathways and mechanisms of action.

Pathogenic variant in EPHB4 results in central conducting lymphatic anomaly.

Central conducting lymphatic anomaly (CCLA) is one of the complex lymphatic anomalies characterized by dilated lymphatic channels, lymphatic channel dysmotility and distal obstruction affecting lymphatic drainage. We performed whole exome sequencing (WES) of DNA from a four-generation pedigree and examined the consequences of the variant by transfection of mammalian cells and morpholino and rescue studies in zebrafish. WES revealed a heterozygous mutation in EPHB4 (RefSeq NM_004444.4; c.2334 + 1G>C) and RNA-Seq demonstrated that the EPHB4 mutation destroys the normal donor site, which leads to the use of a cryptic splice donor that results in retention of the intervening 12-bp intron sequence. Transient co-expression of the wild-type and mutant EPHB4 proteins showed reduced phosphorylation of tyrosine, consistent with a loss-of-function effect. Zebrafish ephb4a morpholino resulted in vessel misbranching and deformities in the lymphatic vessel development, indicative of possible differentiation defects in lymphatic vessels, mimicking the lymphatic presentations of the patients. Immunoblot analysis using zebrafish lysates demonstrated over-activation of mTORC1 as a consequence of reduced EPHB4 signaling. Strikingly, drugs that inhibit mTOR signaling or RAS-MAPK signaling effectively rescued the misbranching phenotype in a comparable manner. Moreover, knock-in of EPHB4 mutation in HEK293T cells also induced mTORC1 activity. Our data demonstrate the pathogenicity of the identified EPHB4 mutation as a novel cause of CCLA and suggesting that ERK inhibitors may have therapeutic benefits in such patients with complex lymphatic anomalies.

Miescher’s cheilitis: A case report with literature review

Miescher’s cheilitis is an inflammatory disorder characterized by chronic lip swelling due to granulomatous inflammation. It is rare disorder first described by Miescher in 1945. It is monosymptomatic form of Melkersson-Rosenthal syndrome. We report a case of Miescher’s cheilitis in a 59-year old lady presented with recurrent swelling and erythema of upper lip and submental area with no features of facial palsy and fissuring of tongue. Laboratory tests including serum complement C3, C4 and C1 esterase inhibitor functional were within normal limits. The biopsy from the upper lip revealed dermal edema, dilated lymphatic channels and multiple granulomas. After exclusion of other causes of orofacial granulomatosis, the diagnosis of Miescher’s cheilitis was made. Patient was treated with oral hydroxychloroquine and topical tacrolimus and mometasone cream with gradual improvement.

Jejunal Lymphangiectasia as Source of Obscure Gastrointestinal Bleed (GIB) and Its Endoscopic Management

Intestinal lymphangiectasia is a pathologic dilatation of the intestinal lymphatic vessels in the mucosal and sub-mucosal layers of the gastrointestinal tract. Protein loosing enteropathy is a common presentation, gastrointestinal bleeding is unusual. A 36-year-old woman with a history of gastroesophageal reflux disease was evaluated for a 3-month history of melena, 20 lb. weight loss, and fatigue. Physical examination revealed generalized pallor and mild non-rebound tenderness in the left upper quadrant. Laboratory data revealed macrocytic anemia with hemoglobin (Hgb) of 5.7 g/dl, MCV of 106 and reticulocyte count of 12.9%. Iron studies revealed iron deficiency anemia and anemia of chronic disease. Celiac panel was unremarkable. She refused blood transfusions due to religious beliefs. Given the presence of anemia, the patient underwent esophagogastroscopy and colonoscopy, both were unremarkable. She was started on subcutaneous darbepoetin and intravenous iron which initially improved her Hb to 7.0 g/dl but her fatigue and melena recurred. Capsule endoscopy showed mucosal changes compatible with lymphangiectasia with multiple areas of active bleeding with clots within the first two hours of the capsule endoscopy. Single balloon enteroscopy showed a 10-cm segment of extensive whitish linear plaques with polypoidal areas with slow oozing of blood in the proximal jejunum (Figure 1). Argon plasma coagulation (Figure 2) was used to achieve hemostasis successfully. Biopsy from the polypoidal whitish plaques were consistent with lymphangiectasia (Figure 3). Post procedure, her melena resolved and Hgb improved to 11.1g/dl with intravenous iron. Intestinal lymphangiectasia presenting with isolated GI bleed is very rare. Only a few case reports have been reported in the literature. To our knowledge, this is the first case reported in literature using APC as a treatment modality for actively bleeding biopsy proven lymphangiectasia.Figure: Jejunal lymphangiectasia with active bleeding.Figure: Argon plasma coagulation used to achieve hemostasis in jejunal lymphangiectasia.Figure: Jejunal mucosa with dilated lymphatic channels in lamina propria filled with protein-rich fluid.

Histological Assessment of the Carotid Sheath in Patients With Oral Squamous Cell Carcinoma

During surgical management of the neck using various types of neck dissection, the carotid sheath is removed, in particular, the part adjacent to the jugular lymph node chain, with the intention of preventing recurrence from the lymphatics present within it. The role of the carotid sheath as a potential origin for nodal recurrence has not been proved thus far. Working in a tissue plane between the carotid sheath and the neurovascular structures of the neck can lead to a greater chance of damage to these structures. Also, the carotid sheath is a strong fibroelastic tissue barrier that shields the internal jugular vein and carotid artery from saliva and local infection during the postoperative period. Thus, this study investigated the histopathology of the carotid sheath in patients with oral squamous cell carcinoma (OSCC) and assessed the pathologic infiltration of the carotid sheath when grossly uninvolved. Pathologic infiltration and histopathologic characteristics of the entire length of the carotid sheath were assessed in 30 biopsy-proved cases of OSCC; these patients underwent surgical excision of the lesion in addition to neck dissection from 2013 to 2015 in the craniofacial unit of the authors' institution. The carotid sheath consisted of fibrofatty tissue and interspersed nerve bundles. Neutrophilic infiltration and dilated lymphatic channels were seen in all 30 cases. Miniature lymph nodes adherent to the carotid sheath were seen in 5 cases and some lymphoid aggregates were seen in 15 cases. The carotid sheath in all 30 cases (metastatic and nonmetastatic) was free from tumor deposit and lymphatic tumor emboli, which are indicators of tumor cell infiltration. Indicators of tumor cell infiltration were not found in any of the 30 cases. The result did not vary with the age or gender of the patient, tumor size, location, staging or grading of the tumor, or even when there were metastatic lymph nodes in the gross specimen. Hence, the role of the carotid sheath as a potential origin for nodal recurrence is questionable and its removal needs reconsideration.

Diffuse Pulmonary Lymphangiomatosis: MDCT Findings After Direct Lymphangiography.

The aim of this study was to analyze the findings of MDCT performed after direct lymphangiography in patients with diffuse pulmonary lymphangiomatosis. Twenty-three patients (13 male and 10 female patients) diagnosed with diffuse pulmonary lymphangiomatosis on the basis of clinical features and findings from imaging, bronchoscopy, and pathologic analysis were retrospectively evaluated. All patients underwent pulmonary MDCT after direct lymphangiography, surgical operation or open lung biopsy, and histopathologic examination. MDCT images were analyzed by two experienced radiologists independently. MDCT after direct lymphangiography revealed numerous intrathoracic abnormalities, including abnormal distribution of contrast medium, dilatation of lymphatic channels, mediastinal soft-tissue infiltration, and peribronchovascular thickening. Nineteen patients had interlobular septal thickening, 18 had diffuse ground-glass opacities, 22 had pleural effusion, 14 had extrapleural soft-tissue thickening, 20 had pericardial effusion and thickened pericardium, 10 had multiple lymphadenopathy in mediastinum, and five had mediastinal, pericardial, and thoracic aeroceles. MDCT performed after direct lymphangiography is well suited to clarify the characteristics of intrathoracic disorders and is an excellent tool in the diagnosis of diffuse pulmonary lymphangiomatosis.