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Soft tissue

Vascular

Benign

Lymphangioma

Author: Farres Obeidin, M.D.

Editorial Board Member: Nasir Ud Din, M.B.B.S.

Deputy Editor-in-Chief: Borislav A. Alexiev, M.D.

Last author update: 1 June 2023

Last staff update: 1 June 2023

Copyright: 2002-2023, PathologyOutlines.com, Inc.

PubMed Search: Lymphangioma

See Also: Cystic, Lymphangiomatous papules / plaques postradiation

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Table of Contents

Cite this page: Obeidin F. Lymphangioma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissuelymphangioma.html. Accessed June 9th, 2023.

Definition / general

Benign localized or diffuse vascular proliferation composed of lymphatic vessels

Essential features

Developmental proliferation composed of lymphatic vessels of varying sizes
May be either microcystic or macrocystic in nature
Wide age range but predominant in children and young adults
Histology: dilated, thin walled lymphatic channels with flat endothelial cells; may show prominent stromal lymphoid tissue and proteinaceous fluid
IHC: PROX1, CD31, D2-40 and VEGFR3 positive

Terminology

Updated 2018 ISSVA classification for vascular anomalies recommends using the term lymphatic malformation for all lymphatic anomalies
Related / previous terminology: cystic hygroma, lymphangioma, lymphangioma circumscriptum, cavernous lymphangioma, intra-abdominal cystic lymphangioma, hemangiolymphangioma

ICD coding

ICD-10: D18.1 - lymphangioma, any site

Epidemiology

Wide age range
Majority are in children and young adults (90% diagnosed by age 2)
Mean age is 3.3 years (J Pediatr Surg 1999;34:1164)
Slight male predominance

Sites

May be superficial or deep (Semin Intervent Radiol 2017;34:225)
Macrocystic
- Often in skin, subcutaneous tissue or deeper
- Commonly neck and groin in infants with chromosomal abnormalities
Microcystic
- Most commonly in skin and mucosal sites

Pathophysiology

Multiple theories suggested for the pathogenesis, including
- Sequestration of lymphoid tissue during development
- Abnormal budding of lymphatic vessels during development
- Lack of fusion of the lymphatic system to the venous system
- Trauma / infection
Various vascular growth factors are associated with the genesis of lymphangiomas (Virchows Arch 2008;453:1)

Etiology

Many lymphatic malformations show somatic mutations in PIK3CA (J Pediatr 2015;166:1048)
Macrocystic lymphatic malformations (cystic hygroma) may be associated with both euploid and aneuploid fetuses, including trisomy 21, trisomy 18, trisomy 13, Turner syndrome and Noonan syndrome (Acta Obstet Gynecol Scand 2007;86:1442)

Diagrams / tables

Table 1: Nomenclature for vascular anomalies

Vascular tumors	Vascular malformations
Benign Locally aggressive or borderline Malignant	Simple	Combined
Benign Locally aggressive or borderline Malignant	Capillary malformations Lymphatic malformations Venous malformations Arteriovenous malformations Arteriovenous fistula	Combination of capillary, venous, lymphatic or arterial vessels; for example Capillary venous malformation Capillary lymphatic malformation Lymphatic venous malformation

Adapted from the 2018 ISSVA classification for vascular anomalies (ISSVA: Classification for Vascular Anomalies [Accessed 6 December 2022])
Nomenclature may also include the name of major vessels or syndromes when associated with other anomalies

Clinical features

In the skin, pale and pink vesicles
Deep lesions are circumscribed, soft, fluctuant and painless swellings
Large cystic lesions may cause compression of adjacent structures

Diagnosis

Clinical history and imaging studies can suggest a lymphangioma
Usually diagnosed on simple excision or incidentally on biopsy

Radiology description

Considered a low flow vascular malformation
Usually cystic in appearance but hemorrhage or infection may give a more solid appearance
Ultrasound (AJR Am J Roentgenol 2004;182:1485)
- Multilocular cystic masses with anechoic cyst contents or echogenic debris
- Can have wide variation
CT
- Homogenous and cystic with low attenuation
- Often does not show the intrinsic septations
MRI (AJR Am J Roentgenol 2004;182:1485)
- Septated, lobulated mass with fluid-fluid levels; may infiltrate tissue planes
- Low signal intensity on T1, high signal intensity on T2
- Macrocystic tumors may have rim and septal enhancement that are not seen in microcystic tumors

Radiology images

Images hosted on other servers:

Retroperitoneal lymphatic malformation CT

Mesenteric mass MRI

Prognostic factors

Benign with a generally excellent prognosis in adults
Locally recurrent potential (~20% of tumors); younger age and presence of associated symptoms of infection, dyspnea, dysphagia or hemorrhage are associated with higher rates of recurrence (Arch Otolaryngol Head Neck Surg 1997;123:1061)
Neonatal / congenital and macrocystic tumors have a poor prognosis depending on the associated genetic and clinical anomalies (Arch Gynecol Obstet 2007;276:491, Eur J Obstet Gynecol Reprod Biol 2005;118:40)

Case reports

Neonate with giant abdominal lymphatic malformation diagnosed at 18 weeks gestation (J Surg Case Rep 2020;2020:rjaa252)
3 year old boy with a right upper lip swelling (Pediatr Dermatol 2019;36:967)
16 year old boy with generalized subcutaneous swelling over the lower back (Radiol Case Rep 2020;16:66)
18 year old man with multiple verrucous lesions of the right hand (Pediatr Dermatol 2013;30:e78)
21 year old pregnant woman with difficulty breathing and a mass found in the nasopharynx (Am J Case Rep 2019;20:868)
24 year old woman with a dorsal tongue mass (Head Neck Pathol 2020;14:512)
29 year old woman with a large intra-abdominal / retroperitoneal mass (Radiol Case Rep 2020;16:123)

Treatment

Depends heavily on the clinical presentation, size and location
Small or localized lesions are generally amenable to surgical resection
Large lesions involving multiple deep structures or tissue planes are often not surgically resectable
Sclerotherapy has been used to some success; particularly in macrocystic lymphatic malformations (Semin Pediatr Surg 2014;23:178)
Sirolimus may be used to improve prognosis in lymphatic malformations that are life threatening or refractory to other therapies (J Vasc Surg 2020;71:318)

Clinical images

Images hosted on other servers:

Lymphangioma circumscriptum

Multiple vesicular papules

Cystic hygroma

Gross description

Multicystic and spongy, containing watery / milky chylous fluid

Gross images

Contributed by Nasir Ud Din, M.B.B.S.

Cystic lymphangioma

Images hosted on other servers:

Multiloculated soft tissue mass

Microscopic (histologic) description

Divided into categories of macrocystic, microcystic or combined based on the size of the lymphatic channels
Macrocystic includes cystic hygroma / cystic lymphangioma
Microcystic includes lymphangioma circumscriptum, cutaneous and small mucosal lymphatic malformations
Thin walled, dilated lymphatic channels with or without intraluminal proteinaceous material and lymphocytes
Composed of bland, flat endothelial cells
Stroma / lymphatic walls may show aggregates of lymphocytes
Cutaneous tumors may have overlying epidermal hyperplasia
Larger lymphatic channels can have smooth muscle in the walls
Longstanding lesions have stromal inflammation, fibrosis, xanthogranulomatous inflammation and myofibroblastic proliferation, particularly in mesenteric and retroperitoneal locations (Hum Pathol 2005;36:426)
Can cross tissue planes, dissect around normal structures and have anastomosing growth pattern (lymphangiomatosis)

Microscopic (histologic) images

Contributed by Farres Obeidin, M.D.

Colonic lymphatic malformation

Skin lymphatic malformation

Dilated lymphatic channels

Lymphoid stroma

Stromal fibrosis

Lymphaticovenous malformation

D2-40

Positive stains

PROX1, VEGFR3 and CD31 (consistently in small and large vessels); D2-40 / podoplanin (consistent in small vessels but may be lost in large vessels) (Pediatr Dev Pathol 2009;12:187)
CD34 (variable)
LYVE1
SMA highlights the smooth muscle in the walls of the vessels (Mod Pathol 2000;13:1128)

Molecular / cytogenetics description

Can show somatic mutations in PIK3CA or association with PIK3CA related overgrowth syndromes (J Pediatr 2015;166:1048)

Sample pathology report

Abdominal mass, excision:
- Lymphatic malformation, mixed macrocystic and microcystic (see comment)
- Comment: Microscopic sections demonstrate small to large caliber vascular spaces filled with proteinaceous fluid and are surrounded by extensive lymphocytic inflammation. The endothelial cells are flat without nuclear atypia and are highlighted with a D2-40 immunostain, supporting the diagnosis.

Differential diagnosis

Benign vascular neoplasms / malformations:
- Lymphatic vessels may be present alone in a lymphatic malformation or with other vessel types
- Artery is typically thicker walled with an internal elastic lamina
- Vein has a muscular wall without an elastic lamina
- Arteries and veins stain with ERG, CD34 and CD31 but not PROX1 or D2-40
Papillary intralymphatic angioendothelioma:
- Typically arises in a background of lymphatic malformation
- Defined by tufting and hobnailing endothelial cell proliferation into the lymphatic channels
Retiform hemangioendothelioma:
- Positive for vascular markers and PROX1, usually negative for D2-40
- Retiform / arborizing architecture with hobnail luminal cells
Angiosarcoma:
- Cytologic atypia with anastomosing, infiltrative architecture and mitotic activity

Additional references

WHO Classification of Tumours Editorial Board: Soft Tissue and Bone Tumours, 5th Edition, 2020

Board review style question #1

A 55 year old woman is undergoing a routine screening colonoscopy, which demonstrates a 0.3 cm sessile nodule in the ascending colon. A biopsy is taken and the histology is represented by the picture above. Which of the following immunohistochemical panels would be expected to stain the lesional cells?

D2-40, PROX1, CD31
ERG, FLI1, CD34
HHV8
p53, AE1 / AE3

Board review style answer #1

A. D2-40, PROX1, CD31. The picture represents a benign lymphatic malformation / lymphangiomatosis in a colon polyp. These tumors may be infiltrative throughout the lamina propria but overall have a benign cytology and stain with lymphatic endothelial cell markers (D2-40, PROX1, CD31, LYVE1).

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Reference: Lymphangioma

Board review style question #2

Macrocystic lymphatic malformations (cystic hygroma) are commonly seen in neonates with which of the following syndromes?

Beckwith-Wiedemann syndrome
Fragile X syndrome
Meckel-Gruber syndrome
Noonan syndrome

Board review style answer #2

D. Noonan syndrome. Cystic hygromas are commonly seen in aneuploidy syndromes like trisomies and Turner syndrome; however, they may also commonly be seen in some euploid fetuses, particularly those with Noonan syndrome.

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Reference: Lymphangioma

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