Soft tissue
Benign vascular tumors
Glomus tumor

Author: Farres Obeidin, M.D.
Senior Author: Boris Alexiev, M.D.
Editorial Board Member Review: Michael R. Clay, M.D.
Editor-in-Chief Review: Debra Zynger, M.D.

Revised: 29 November 2018, last major update October 2018

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed search: Glomus tumor [title] soft tissue

Related topics: Symplastic glomus tumor

Page views in 2018: 29,456
Page views in 2019 to date: 8,675
Cite this page: Obeidin F, Alexiev B. Glomus tumor. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/softtissueglomus.html. Accessed March 19th, 2019.
Definition / general
  • Mesenchymal tumor composed of modified smooth muscle cells arising from the glomus body
Essential features
  • Predominantly cutaneous, most common in subungual region of the finger but may occur anywhere
  • Usually benign with very rare malignant variants
  • Combination of glomus cells, smooth muscle cells and vasculature
  • Round, punched out nuclei with amphophilic to eosinophilic stroma surrounding branching, capillary sized vessels
  • Positive for SMA, MSA, calponin, h-caldesmon, collagen type IV; negative for cytokeratin and S100
Terminology
  • Name differs based on morphology: glomus tumor, glomangioma, glomangiomyoma and glomangiomatosis
  • Malignant glomus tumors are also called glomangiosarcoma
  • Note: certain site specific misnomers like glomus faciale, glomus jugulare, glomus tympanicum, glomus vagale, etc. are actually paragangliomas (N Engl J Med 2002;347:854)
  • Glomangiopericytoma may be used for glomus tumors with prominent hemangiopericytic vasculature; however, these tumors are different from the pericytic site specific sinonasal glomangiopericytoma
ICD coding
  • D21.10: Other benign neoplasms of connective and other soft tissue
Epidemiology
Sites
  • Described throughout the body; most common is upper extremity (62%), particularly the fingers (27%)
  • Subungual region is the most common location on the finger
  • Other sites:
    • Trunk wall (11%)
    • Internal (11%)
    • Lower extremity (9%)
    • Head and neck (7%)
  • Atypical and malignant glomus tumors are more commonly deep-seated than benign tumors (Am J Surg Pathol 2001;25:1)
Pathophysiology
  • NF1 associated tumors arise from bi-allelic inactivation of NF1 (Cancer Res 2009;69:7393)
    • Loss of neurofibromin in glomus cells leads to activation of the RAS-MAPK pathway
  • Familial glomus tumors (glomuvenous malformations) are caused by inactivating mutations in the glomulin gene expressed in vascular smooth muscle cells (Am J Hum Genet 2013;92:188)
  • Some cases show novel translocation resulting in oncogenic activation of NOTCH driven by translocation with the MIR143 promoter (Genes Chromosomes Cancer 2013;52:1075)
Etiology
  • Arises from the Sucquet-Hoyer canal of the glomus body, a specialized arteriovenous anastomosis that regulates heat in the skin and is surrounded by layers of epithelioid, SMA+ glomus cells
  • Cold temperature causes relaxation of the glomus cells to open the anastomosis and divert blood away from the capillary network to conserve body heat (J Med Genet 2010;47:525)
Clinical features
  • Symptoms:
    • Paroxysms of pain radiating away from the lesion, often out of proportion to the size of the neoplasm
    • Pain can be elicited by changes in temperature or tactile stimulation
    • Can be accompanied by hypesthesia, muscle atrophy or osteoporosis
  • Some glomus tumors of the fingers and toes are associated with NF1 (J Med Genet 2010;47:525)
Radiology description
  • MRI: well defined mass, dark on T1 and bright, contrast enhancing on T2 or T1 post gadolinium fat saturation images
  • MR angiography: strong enhancement in the arterial phase and tumor blush, which increases in size in the delayed phase
  • Ultrasound: solid, hypoechoic mass with possible associated erosion of the underlying bone (Radiographics 2010;30:1621)
  • Radiography: may show thinning of the cortical bone in subungual tumors (AJR Am J Roentgenol 2004;182:263)
Radiology images

Images hosted on PathOut server:

Contributed by Farres Obeidin, M.D.

Leg mass


Duodenal mass

Wrist mass

Subungual mass

Prognostic factors
  • Benign tumors have a small chance for recurrence if incompletely excised
  • Atypical features found to correlate with adverse outcome, can be called glomus tumor of uncertain malignant potential:
    • Deep location, size > 2 cm and the presence of atypical mitotic figures
    • Necrosis, mitotic activity > 5/50 high powered fields and the combination of high nuclear grade and high mitotic activity showed a trend but was not found to be significant
  • Malignant glomus tumors are characterized by (1) marked nuclear atypia and any level of mitotic activity or (2) atypical mitotic figures and metastasize in up to 40% of cases (Am J Surg Pathol 2001;25:1)
Case reports
Treatment
  • Benign tumors cured by complete surgical excision; recurrence rate of 10% likely due to incomplete resection (Arch Pathol Lab Med 2008;132:1448)
  • Direct transungual excision is the standard but can cause nail deformity; lateral subperiosteal approach reduces risk of nail deformity but may slightly raise risk of recurrence (Plast Reconstr Surg 2004;114:1486)
  • No clinical trial data is available for treatment of malignant glomus tumors, but doxorubicin and olaratumab have been approved for recurrent / metastatic disease
  • No prospective data exists yet for Notch inhibition or immune checkpoint inhibitors
Clinical images

Images hosted on other servers:
Missing Image

Nail discoloration

Fullness in posterior nail fold region

Glomus tumor during exploration

Missing Image

Tumor resection

Gross description
  • Bulging mass with an irregular, nodular hemorrhagic cut surface
  • Superficial lesions typically < 1.0 cm
Gross images

Images hosted on PathOut server:

Contributed by Farres Obeidin, M.D.

Leg mass



Images hosted on other servers:

Liver tumor

Microscopic (histologic) description
  • Well circumscribed mass composed of 3 components: glomus cells, vasculature and smooth muscle cells
  • Solid glomus tumor (75% of cases): predominantly glomus cells, poor vasculature and rare smooth muscle cells
  • Glomangioma (20% of cases): tumors with prominent vascular component
  • Glomangiomyoma (5% of cases): tumors with prominent vascular and smoot muscle components
  • Rare variants have microscopically infiltrative and diffuse growth and are known as glomangiomatosis
  • Benign glomus tumors (Arch Pathol Lab Med 2008;132:1448):
    • Branching capillary sized vessels lined by endothelial cells surrounded by collars of uniform glomus cells forming nests, sheets and trabeculae in a hyalinized or myxoid stroma
    • Glomus cell has a round shape with indistinct borders with a rounded, sharply punched out nucleus in an amphophilic to eosinophilic cytoplasm
    • Chromatin is homogenous and bland with inconspicuous nucleoli
    • Very rare mitoses
  • Symplastic glomus tumor:
    • Marked nuclear atypia with no mitotic activity or other atypical features
    • Does not affect prognosis
  • Malignant glomus tumor (Am J Surg Pathol 2001;25:1):
    • Diagnosis should be reserved for tumors showing (1) marked nuclear atypia and any level of mitotic activity or (2) atypical mitotic figures
    • May be spindled and resemble leiomyosarcoma / fibrosarcoma or may consist of sheets of malignant appearing round cells
    • Benign glomus tumor component can often be found at the periphery and help with diagnosis
  • Glomus tumor of uncertain malignant potential:
    • Tumors that do not fulfill criteria for malignancy but have at least 1 atypical feature other than nuclear pleomorphism
    • Atypical features include deep location, size ≥ 2 cm and mitotic activity > 5 mitoses/50 high powered fields
  • Oncocytic features have been described (Histopathology 1987;11:523)
Microscopic (histologic) images

Images hosted on PathOut server:

Contributed by Farres Obeidin, M.D.

Well circumscribed

Sheets of cells

Spindling

Myxoid stroma

Round, bland cells

Nuclear inclusions


Glomangioma

Glomangiomyoma


Malignant glomus tumor

SMA

Glomus body



Case of the Week #289:

Glomangioma

SMA

CD31

Cytology description
  • Cohesive clusters of uniform round cells with scanty cytoplasm
  • Background of scattered amorphous magenta colored material, blood and occasional inflammatory cells (J Cytol 2010;27:104)
Cytology images

Images hosted on PathOut server:

Malignant glomus tumor



Images hosted on other servers:

FNA

Positive stains
Electron microscopy description
  • Thick basal lamina surrounds individual glomus cells except at cellular junctions
  • Pinocytic vesicles and myofibrils with dense bodies in the cytoplasm (Cancer 1969;23:1176)
Electron microscopy images

Images hosted on other servers:
Missing Image

Thickened basal lamina

Molecular / cytogenetics description
Molecular / cytogenetics images

Images hosted on other servers:
Missing Image

MIR143-NOTCH2 fusion

Differential diagnosis
Board review question #1

    Which of the following statements about this lesion is true?

  1. Complete surgical excision is curative
  2. It may metastasize in about 30% of cases
  3. It will show diffuse positivity for CD34, CD31 and ERG
  4. The most common location is in the ankle
Board review answer #1
A. This is a glomangioma, a variant of glomus tumor. It is a benign tumor and, if completely excised, surgical excision is essentially curative. The most common location is in the subungual region of the finger. Though it may show focal positivity for CD34, the staining for CD31 and ERG will be negative as the tumor cells are not vascular in origin.

Comment Here
Board review question #2
    Which of the following molecular aberrations can be seen in glomus tumors?

  1. ETV6-NTRK3
  2. EWSR1-FLI1
  3. MIR143-NOTCH1
  4. SS18-SSX2
Board review answer #2
C. Over 50% of glomus tumors harbor gene fusions of MIR143 with either NOTCH1 or NOTCH2.

Comment Here
Back to top