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Soft tissue

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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

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Table of Contents

Cite this page: Warmke L, Meis J. Cystic / cavernous lymphangioma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissuelymphangiomacystic.html. Accessed February 3rd, 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:
- 9170/0 - lymphangioma, NOS
- 9173/0 - cystic lymphangioma
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

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

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

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

Negative stains

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

WHO Classification of Tumours Editorial Board: Soft Tissue and Bone Tumours, 5th Edition, 2020, Lindberg: Diagnostic Pathology - Soft Tissue Tumors, 2nd Edition, 2015

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

D. Turner syndrome

Comment Here

Reference: Cystic / cavernous lymphangioma

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

C. D2-40

Comment Here

Reference: Cystic / cavernous lymphangioma

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