Soft tissue
Vascular
Benign
Cystic / cavernous lymphangioma
Authors: Laura Warmke, M.D., Jeanne Meis, M.D.
Editorial Board Member: Jose G. Mantilla, M.D.
Deputy Editor-in-Chief: Borislav A. Alexiev, M.D.
Last author update: 29 November 2022
Last staff update: 29 November 2022
Copyright: 2002-2023, PathologyOutlines.com, Inc.
PubMed Search: Cystic / cavernous lymphangioma
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Videos | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Warmke L, Meis J. Cystic / cavernous lymphangioma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissuelymphangiomacystic.html. Accessed November 29th, 2023.
Definition / general
- Benign vascular lesion composed of a collection of dilated lymphatic channels that may be superficial, deep or diffusely involve organ systems
- First described by Rodender in 1828 (Arch Pathol Lab Med 2015;139:278)
Essential features
- Benign proliferation of lymphatic vessels
- Immunohistochemical expression of CD31 and D2-40
Terminology
- Lymphatic malformation
- Lymphangioma circumscriptum (superficial cutaneous lymphangioma)
- Cavernous lymphangioma (deep lymphangioma)
- Cystic hygroma (cystic lymphangioma)
- Intra-abdominal cystic lymphangioma
- Hemangiolymphangioma
- Lymphangiomatosis (generalized lymphangioma, systemic angiomatosis)
ICD coding
- ICD-O:
- ICD-11:
- LA90.12 & XH9MR8 - lymphatic malformations of certain specified sites & lymphangioma, NOS
- 2E81.10 - disseminated lymphangiomatosis
Epidemiology
- Primarily occurs in children and young adults
- Majority presents at birth or within first couple of years (~90%) (J Pediatr Surg 1999;34:1164)
- Intra-abdominal lesions have a slight male predominance
- Cystic hygroma may occur in association with Turner syndrome (Hum Pathol 1984;15:61)
- Splenic lymphangiomas may occur with Klippel-Trenaunay syndrome (J Vasc Surg 2006;43:848)
- Associated with variant of Maffucci syndrome (J Pediatr Orthop B 2003;12:147)
- Associated with trisomies 13, 18 and 21 and other genetic syndromes (e.g., Noonan)
- Rare cases can occur in older adults, often mesenteric lesions (Arch Surg 1985;120:1266, Pathol Oncol Res 2000;6:146, BMJ Case Rep 2011;2011:bcr0320114022)
Sites
- Superficial lesions frequently involve the skin of proximal extremities / limb girdles (Br J Dermatol 1976;94:473)
- Deep lesions frequently involve the head and neck (primarily tongue and floor of mouth), followed by the extremities, axilla, groin and abdominal region (J Pediatr Surg 1999;34:1164, Virchows Arch 2008;453:1, Hum Pathol 2005;36:426)
- Cystic hygroma commonly involves head and neck, usually posterior triangle of neck
- Intra-abdominal lesions involve mesentery, omentum and retroperitoneum
- Lymphangiomatosis can involve multiple sites (e.g., liver, lungs and bone) (Am J Surg Pathol 1995;19:125, J Bone Joint Surg Am 2005;87:162, J Pediatr Hematol Oncol 2004;26:136)
Pathophysiology
- Arises from abnormal lymphatic system development
- PIK3CA and other mutations thought to drive the process through endothelial growth receptor pathways (J Pediatr 2015;166:1048, Int J Clin Exp Pathol 2015;8:5924)
Etiology
- Early or congenital lesions are favored to be developmental malformations
- Sequestered lymphatics fail to communicate with normal lymphovascular system
- Most are considered to be malformations / hamartomas (not true neoplasms)
- Genetic abnormalities play a role (Virchows Arch 2008;453:1)
Clinical features
- Superficial lesions may present as multiple small, grouped vesicular lesions involving the skin
- Tongue lesions present as a mass surfaced by pebbly, vesicle-like nodules said to resemble frog eggs (Head Neck Pathol 2020;14:512)
- Cystic hygroma usually presents as a unilateral, diffuse, nonpulsatile, painless swelling of the posterior cervical triangle
- Deeper lesions may present as a large, slow growing painless mass
- Intra-abdominal lesions can displace organs and cause intestinal obstruction
Diagnosis
- Swollen soft tissue mass with positive transillumination test
- Ultrasound can confirm cystic or multicystic lesion
- Diagnosing these lesions may be very challenging in small biopsies given their cystic nature and bland cytologic features
Radiology description
- Xray:
- Abdominal lesions commonly present as a soft tissue mass with displacement of bowel loops (Pediatr Radiol 2002;32:88)
- Ultrasound:
- Unilocular or multilocular anechoic mass
- Sharply defined cystic of multicystic mass with internal septations
- May be diagnosed on prenatal ultrasound (Prenat Diagn 1988;8:405)
- CT findings:
- Nonenhancing cystic lesions
- Septated cystic mass of variable size (Pediatr Radiol 2002;32:88)
- Contains fluid of homogeneous density
- May displace adjacent organs
- MRI findings:
- T1 weighted image may be hypointense or hyperintense when filled with hemorrhage or proteinaceous material (Magn Reson Imaging 2003;21:81)
- T2 weighted image shows a multiloculated mass with hyperintense areas
Radiology images
Contributed by Jeanne Meis, M.D.
Radiograph of left lower extremity
Angiogram of
lymphangiomatosis
MRI of left extremity
MRI of lower abdomen
Radiograph of lower extremity
MRI of mediastinal lymphangioma
Radiograph of mediastinal lymphangioma
Arteriogram of lymphangioma
Images hosted on other servers:
CT of splenic lymphangioma
CT of orbital lymphangioma
Ultrasound of mesenteric lymphangioma
Prognostic factors
- Benign lesions with excellent prognosis
- Recurrence is high with incomplete removal
- When involving deeper tissue planes, lesions can recur in up to 20% of patients (J Pediatr Surg 1992;27:220)
- Complications include infection, hemorrhage, rupture and intestinal obstruction
- Diffuse lymphangiomatosis with mediastinal or visceral organ involvement can be fatal
- No malignant transformation has been reported
Case reports
- 13 year old boy with cystic hygroma of the neck (Rom J Morphol Embryol 2021;62:845)
- 24 year old woman with lymphangioma of the dorsal tongue (Head Neck Pathol 2020;14:512)
- 34 year old woman with jejunal cavernous lymphangioma (BMJ Case Rep 2011;2011:bcr0320114022)
Treatment
- Surgical resection may be indicated for large, symptomatic lesions
- Intralesional injection of sclerosing agents, including bleomycin and OK-432
- Radiofrequency ablation (Int J Pediatr Otorhinolaryngol 2008;72:953)
Clinical images
Contributed by Jeanne Meis, M.D.
Lower extremity
Images hosted on other servers:
Cystic hygroma of neck
Lymphangioma of dorsal tongue
Omentum: 30 cm tumor in 4 year old girl
Scrotal tumor with hemorrhage in 3 year old boy
Abdominal cyst: 25 cm
Broad ligament: 19 kg tumor in 70 year old woman
Mesentery: 1 year old boy
Thigh tumor
Mesenteric tumor: 12 year old girl
Mesenteric tumors
Mesenteric tumors
Gross description
- Multicystic and spongy lesions
- Reddish / brown translucent cystic mass
- Cystic spaces often contain watery, thick or milky fluid (Hum Pathol 2005;36:426)
Gross images
Contributed by Jeanne Meis, M.D.
Resection of lymphangiomatosis
Mediastinal lymphangioma
Images hosted on other servers:
Splenic lymphangioma
Microscopic (histologic) description
- Variably sized, thin walled, dilated lymphatic vessels lined by flattened endothelium
- Frequently surrounded by lymphoid aggregates, sometimes with reactive germinal centers
- Lumina may contain eosinophilic and amorphous proteinaceous fluid with occasional lipid laden macrophages and lymphocytes
- Longstanding lesions may show interstitial fibrosis
- Walls of larger vessels may contain smooth muscle
- Stromal mast cells and hemosiderin deposits are frequently seen
- Lining of the cysts may rarely form papillary projections
- Lymphangiomatosis frequently shows an anastomosing growth pattern, dissecting around normal structures
- Extensive granulation tissue and inflammation may obscure lymphatic nature (Hum Pathol 2005;36:426)
Microscopic (histologic) images
Contributed by Laura Warmke, M.D. and Jeanne Meis, M.D.
Dilated lymphatic spaces
Focal areas of fibrosis
Proteinaceous fluid
Lymphatic channels
Retroperitoneal lymphanagioma
Retroperitoneal lymphanagioma
Lymphangioma circumscriptum
Lymphangioma of tongue
Superficial lymphangioma of vulva
Superficial lymphangioma
Scattered macrophages
Lymphoid aggregate
Lymphoid aggregates
Calcification
Thick wall
Endothelial lining
Irregular vascular channels
Irregular vascular channels
Trichrome stain
D2-40
CD31
Cytokeratin
Virtual slides
Images hosted on other servers:
Lymphangioma involving adrenal gland
Buccal lymphangioma
Positive stains
- Podoplanin (D2-40)
- PROX1 (Am J Surg Pathol 2012;36:351)
- Vascular endothelial growth factor receptor 3 (VEGFR3)
- Lymphatic endothelial hyaluron receptor 1 (LYVE1)
- CD31 and FVIII variable
- CD34 variable (Hum Pathol 2005;36:426)
- SMA positive in smooth muscle in larger vessels
Electron microscopy description
- May assist in determining endothelial origin of cells lining the cysts
- Presence of Weibel-Palade bodies, storage granules of endothelial cells
Molecular / cytogenetics description
- Increased expression of VEGFR3 (Virchows Arch 2008;453:1)
- Mutations in VEGFR3, FLT4, PROX1, FOXC2 and SOX18 may play a role
- Somatic mutations in PIK3CA have been reported (J Pediatr 2015;166:1048)
Videos
Lymphangioma (cystic hygroma)
Sample pathology report
- Soft tissue, retroperitoneal mass, resection:
- Cavernous lymphangioma (see comment)
- Comment: Sections show a lesion composed of dilated lymphatic spaces lined by flattened endothelium without cytologic atypia. Immunohistochemical stains show that the endothelial cells are positive for D2-40 and CD31, supporting a lymphatic nature, while they are negative for cytokeratin. These results, along with the morphologic features, support the above diagnosis.
Differential diagnosis
- Hemangioma:
- Well circumscribed lesion
- Smaller vascular spaces extensively filled with red blood cells
- Vascular malformation:
- Often compressible
- May demonstrate a thrill or bruit
- Atypical vascular lesion:
- Radiation associated
- Frequently occurs in the breast
- Dilated vascular spaces with atypical endothelial cells
- Acquired progressive lymphangioma:
- Cutaneous vascular neoplasm
- Vessels dissect between collagen fibers
- Slow growing reddish brown patch or plaque
- Secondary lymphangiectasia:
- Secondary to lymphatic obstruction
- May be due to tumor, scarring or radiation
- Clinical history is helpful
- Cystic lymphangioma-like adenomatoid tumor (Adv Anat Pathol 2009;16:424):
- Mesothelial in origin
- Positive for cytokeratin and calretinin
- Ultrastructural finding of abundant long, slender microvilli
- Parasitic cyst (echinococcal cyst):
- No true epithelial / endothelial / mesothelial lining
- Protoscolices and refractile hooklets are often present
- Serologic test for Echinococcus are frequently positive
- Mesothelial cyst:
- Positive for cytokeratin and calretinin
- Negative for CD31
Additional references
Board review style question #1
Cystic hygroma (cystic lymphangioma), which frequently involves the posterior triangle of the neck, is associated with which of the following syndromes?
- Down syndrome
- Klippel-Trenaunay syndrome
- Maffucci syndrome
- Turner syndrome
Board review style answer #1
Board review style question #2
Which of the following immunohistochemical stains, when positive, is the most helpful in making the diagnosis of lymphangioma?
- Calretinin
- Cytokeratin
- D2-40
- GLUT1
Board review style answer #2
