Pericytic (perivascular) tumors





Benign tumors


Glomus Tumor


Definition





  • A benign tumor composed of modified smooth muscle cells (e.g., glomus cells)



  • Subclassified into three groups based on the proportions of glomus cells, blood vessels, and (perivascular) smooth muscle cells into:




    • Classical or solid glomus tumor




      • Predominance of glomus cells



      • Blood vessels small and nondistinctive




    • Glomangioma




      • Blood vessels are prominent and dilated



      • Represents the most common variant




    • Glomangiomyoma




      • Prominent smooth muscle component



      • The rarest subtype





  • Pattern of presentation/occurrence




    • Solitary or multiple (localized, plaquelike, disseminated) lesions



    • Sporadically or in the familial setting with autosomal-dominant inheritance pattern



    • Acquired or congenital




  • Multiple tumors generally correspond to glomangioma on histology



Clinical features


Epidemiology





  • Equal gender distribution for solitary and multiple lesions



  • Solitary lesions




    • Wide age distribution



    • Predominance in age groups between 20 and 40 years




  • Multiple lesions (in about 10%)




    • Age of onset typically 10 to 15 years earlier than for solitary lesions



    • Tend to occur predominantly in children



    • Congenital occurrence also reported



    • About two-thirds of the lesions develop by the age of 20 years



    • Presentation in adults uncommon



    • Nonhereditary or hereditary with autosomal-dominant inheritance with incomplete penetrance and variable expressivity



    • Familial glomangiomas, also designated familial glomovenous malformations, have been found to be associated with mutations in the glomulin gene located on chromosome 1p21-22




  • Represents less than 2% of soft tissue tumors



Presentation





  • The triad of symptoms, described by Masson in 1924




    • Excruciating pain out of proportion to the size of the lesion



    • Localized tenderness, reflected by positive Love sign (tenderness to a pinpoint spot with the end of the pencil)



    • Temperature sensitivity, especially for cold, or changes in temperature, precipitating pain




  • Solitary lesions




    • By far predominate (about 90%)



    • Slowly growing papule or nodule with bluish discoloration, plaquelike presentation also reported



    • Less than 1 cm in diameter



    • Predilection for subungual areas of the finger, followed by palm, wrist, forearm, and foot



    • Diverse extracutaneous sites, including gastrointestinal tract (esophagus, stomach, small bowel, colon), respiratory tract (trachea, lungs), mediastinum, bones, and peripheral nerves




  • Multiple lesions




    • Small papules or nodules measuring usually from 0.1 to 0.3 cm and generally not exceeding 3 cm in diameter



    • Plaquelike variant characterized by numerous reddish-blue papules grouped in a single or multiple plaques, and is frequently congenital



    • Average number of lesions from 10 to 20



    • Less often painful than solitary forms



    • Lesions can become painful during the menstrual period or pregnancy, suggesting sensitivity to estrogens



    • Association with diverse conditions has been reported, including multiple endocrine neoplasia (MEN) II syndrome, neurofibromatosis type I, arteriovenous (AV) fistulae, and brachydactyly



    • Predilection for upper limbs




Prognosis and treatment





  • Benign clinical course



  • Complete surgical excision generally curative



  • Recurrences after incomplete/marginal excision from 5% to 50% and tend to be more common at subungual sites



  • Treatment in multiple lesions is directed toward symptomatic ones



  • Other treatment options include laser therapy and sclerotherapy



Pathology


Histology





  • Classical or solid glomus tumor




    • Well-demarcated, unencapsulated proliferation in the dermis/subcutis



    • Nests and/or solid sheets of glomus cells




      • Round to oval, centrally located, uniform nuclei



      • Pale eosinophilic cytoplasm with well-defined borders



      • Mitoses absent or rare



      • Atypical mitoses absent



      • Rare variants consist of cells with epithelioid morphology




    • Vascular component inconspicuous, usually in the form of thin-walled and frequently branching capillaries lined by flat endothelial cells




  • Glomangioma




    • Less circumscribed, occasionally with infiltrative growth in the dermis/subcutis



    • Vascular component prominent



    • Dilated and congested vascular spaces, reminiscent of cavernous hemangioma, lined by a single layer of bland endothelial cells



    • Thrombosis and organization of thrombi with formation of phleboliths not uncommon



    • Glomus cells surround vascular spaces in a single or double layer, multilayering less common




  • Glomangiomyoma




    • Smooth muscle cell component in addition to solid proliferation of glomus cells, the amount of the former component varies and is usually prominent



    • Spindle cells arranged in bundles, fascicles, or display more irregular growth pattern



    • Gradual transition from solid proliferation of glomus cells toward elongated smooth muscle cells (e.g., transitional zone) usually seen




  • Infiltrative glomus tumor




    • Designation for glomus tumors with banal cytology, but infiltrative growth pattern



    • Usually occurs in deep soft tissues




  • Additional histological features




    • Stroma




      • Myxoid/collagenized



      • Can contain scattered nerves



      • Areas of calcification or bone formation uncommon




    • Overlying epidermis generally unremarkable




Immunohistochemistry/special stains





  • Smooth muscle actin, muscle specific actin positive



  • Variable CD34 positivity



  • Desmin usually negative, focal positivity occasionally reported



Genetic profile





  • MIR143 NOTCH fusions are harbored in both benign and malignant glomus tumors, but not other myopericytic tumors; NOTCH 1 (9q34), NOTCH2 (1p31), and less commonly NOTCH3 (19p13.12) can be involved



Main differential diagnoses





  • Eccrine spiradenoma



  • Nodular hidradenoma



  • Vascular tumors



  • Vascular malformations



Classical (solid) glomus tumor



Fig. 1


Classical (solid) glomus tumor.

Well-demarcated and unencapsulated dermal tumor, with tumor cells arranged in solid sheets and small groups/nests.



Fig. 2


Classical (solid) glomus tumor.

Sheetlike proliferation of bland tumor cells. Vascular component is usually inconspicuous and consists of thin-walled vessels.



Fig. 3


Classical (solid) glomus tumor.

Uniform tumor cells with round to oval nuclei and pale eosinophilic cytoplasm.



Fig. 4


Classical (solid) glomus tumor.

The epithelioid variant is characterized by a proliferation of larger tumor cells with more prominent eosinophilic cytoplasm (bottom). A more classical (solid) component occupies the upper part of the picture.



Fig. 5


Classical (solid) glomus tumor,

epithelioid variant—higher magnification.



Fig. 6


Classical (solid) glomus tumor.

Another example of a dermal nodular and solid proliferation of glomus cells, associated with an inconspicuous vascular component.



Fig. 7


Classical (solid) glomus tumor.

Tumor cells with minimal nuclear atypia, small round nuclei, and scant eosinophilic cytoplasm. Note a well-defined cytoplasmic membrane imparting a typical chicken-wire appearance. Mitotic activity is usually absent.



Fig. 8


Classical (solid) glomus tumor.

Tumor cells are usually diffusely positive for smooth muscle actin.




Glomangioma



Fig. 1


Glomangioma.

Note a prominent vascular component, reminiscent of a cavernous hemangioma. Glomus cells are sparse.



Fig. 2


Glomangioma.

Dilated and congested vascular spaces are lined by a single layer of unremarkable endothelial cells. Often, a single layer of glomus cells is seen surrounding vascular structures.




Glomangiomyoma



Fig. 1


Glomangiomyoma.

The hallmark of the entity is an admixture of glomus cells with mature smooth muscle cells. The latter are seen adjacent to or surrounding the vascular spaces. The amount of the smooth muscle component can vary greatly.



Fig. 2


Glomangiomyoma.

Smooth muscle cells merge imperceptibly with more solid proliferation of glomus cells.



Fig. 3


Glomangiomyoma.

Higher magnification delineating a transition from smooth muscle cells to glomus cells (the so-called transitional zone ).




Symplastic Glomus Tumor


Definition





  • A very pale histological variant of glomus tumor displaying areas of cytological atypia and nuclear pleomorphism, not associated with malignancy



  • Nuclear atypia likely degenerative phenomenon and/or related to cellular senescence, with DNA methylation possibly involved in the pathogenesis of the symplastic change



Clinical features


Epidemiology





  • Female predominance (F : M = 3 : 1)



  • Wide age distribution (from 16 to 83 years), most common in the fifth decade



Presentation





  • Slowly growing, tender or painful nodule



  • Pain can be triggered by cold exposure



  • Subungual lesions can be associated with nail deformities



  • Size less than 1 cm in diameter



  • Predilection for fingers, particularly subungual site



Prognosis and treatment





  • Complete local excision generally curative



  • Recurrences rare (up to 13%), usually after incomplete/marginal excision, less likely due to synchronous satellite lesions



Pathology


Histology





  • Nonencapsulated, well-demarcated proliferation in the dermis, with possible extension into the subcutis



  • Areas of classical glomus tumor usually present at the periphery of the proliferation (see earlier)



  • Defining histological feature is polygonal tumor cells with pronounced cytological atypia (e.g., symplastic change), but lacking other features of malignancy




    • Nuclei large and pleomorphic, frequently hyperlobated and bizarre shaped with hyperchromasia, intranuclear cytoplasmic pseudoinclusions, coarse chromatin, and irregular nuclear membrane



    • Mitotic activity generally absent



    • Necrosis absent



    • Pale eosinophilic cytoplasm with indistinct cellular borders




Immunohistochemistry/special stains





  • Smooth muscle actin and CD34 positive



  • Desmin, S100 protein, cytokeratin, CD31, and factor XIIIa negative



  • Ki-67/MIB-1 negative or very low (less than 1% of the tumor cells)


Fig. 1


Symplastic glomus tumor.

This variant of glomus tumor is characterized by prominent nuclear atypia (central part of the picture) in the absence of any other malignancy features, likely representing a degenerative phenomenon.



Fig. 2


Symplastic glomus tumor.

A solid proliferation of epithelioid glomus cells with hyperchromatic nuclei is seen in this area.



Fig. 3


Symplastic glomus tumor.

Another area with epithelioid glomus cells featuring hyperchromatic nuclei.




Glomangiomatosis


Definition





  • Glomangiomatosis is defined as angiomatosis associated with a prominent glomus cell component



Clinical features


Epidemiology





  • Most common in the third decade of life



  • Slightly more common in females



  • Very rare, with fewer than 20 cases reported



Presentation





  • Solitary slowly growing nodule, measuring from 1.5 cm to over 20 cm



  • Lesions at deeper locations (e.g., paravertebral soft tissues) generally larger and more extensive



  • Sites of involvement include lower and upper extremities, head and neck, and chest wall, whereas no lesions reported at subungual site



  • Excruciating pain common



Prognosis and treatment





  • Difficult to remove completely due to the infiltrative growth



  • Surgery represents the primary treatment modality



  • Completeness of excision the most important prognostic parameter for local recurrence(s)



  • Local recurrences in 60%, multiple recurrences in 20%



Pathology


Histology





  • Infiltrative growth pattern typical, with skeletal muscle involvement in over 50%



  • Two main components are glomus cells and large dilated vascular spaces



  • Glomus cells




    • Clusters, sheets, or nodules surrounding and infiltrating anomalous vessel walls



    • Bland cytology (see glomus tumor )




  • Angiomatosis




    • An admixture of blood vessels of different size and caliber




  • Mature fat occasionally represents significant component of the lesion



Immunohistochemistry/special stains





  • Glomus cells




    • Smooth muscle actin and muscle specific actin positive



    • Variable CD34 positivity



    • Desmin usually negative




Main differential diagnoses





  • Glomangioma (distinguish by clinical presentation)



  • Vascular malformation


Fig. 1


Glomangiomatosis.

Low-power magnification reveals the presence of vascular malformation with a typical infiltrative growth pattern.



Fig. 2


Glomangiomatosis.

The entity is characterized by angiomatosis (vascular malformation) associated with a prominent glomus cell component.



Fig. 3


Glomangiomatosis.

Another area depicting intimate association of malformed vessels and glomus cells.



Fig. 4


Glomangiomatosis.

Solid proliferation of glomus cells in the background of vascular malformation.

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Oct 29, 2019 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Pericytic (perivascular) tumors
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