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190 Sangüeza and Requena / Pathology of Vascular Skin Lesions
30. Hisaoka M, Hashimoto H, Iwamasa T. Diagnostic implication of Kaposi’s sarcoma-associated herpes-
virus with special reference to the distinction between spindle cell hemangioendothelioma and Kaposi’s
sarcoma. Arch Pathol Lab Med 1998;122:72–6.
31. Yañez S, Val-Bernal JF, Mira C, Echevarria MA, González-Vela MC, Arce F. Spindle cell hemangioen-
dothelioma associated with multiple skeletal enchondromas: a variant of Maffucci’s syndrome. Gen
Diagn Pathol 1998;143:331–5.
32. Gradner TL, Elston DM. Multiple lower extremity and penile spindle cell hemangioendotheliomas.
Cutis 1998;62:23–6.
33. Bodemer C, Fraitag S, Amoric JC, Benaceur S, Brunelle F, De Prost Y. Hémangioendotheliome à
cellules fusiformes dans une varieté monomelique et multinodulaire chez l’enfant. Ann Dermatol
Venereol 1997;124:857–60.
34. Enjolras O, Wassef M, Merland JJ. Syndrome de Maffucci: une fausse malformation veineusse? Un cas
avec hémangioendothelioma à cellules fusiformes. Ann Dermatol Venereol 1998;125:512–5.
35. Keel SB, Rosemberg AE. Hemorrhagic epithelioid and spindle cell hemangioma: a newly recognized,
unique vascular tumor of bone. Cancer 1999;85:1966–72.
36. Isayama T, Iwasaki H, Ogata K, Naito M. Intramuscular spindle cell hemangioendothelioma. Skeletal
Radiol 1999;28:477–80.
37. Tomasini C, Aloi F, Soro E, Elia V. Spindle cell hemangioma. Dermatology 1999;199:274–6.
38. Setoyama M, Shimada H, Miyazono N, Baba Y, Kanzaki T. Spindle cell hemangioendothelioma:
succesful treatment with recombinant interleukin-2. Br J Dermatol 2000;142:1238–9.
39. Weiss SW, Goldblum JR. Enzinger and Weiss’s Soft Tissue Tumors, 4th ed., St. Louis, Mosby,
2001;853–6.
40. Mentzel T, Kutzner H. Hemangioendotheliomas: heterogeneous vascular neoplasms. Dermatopathol
Pract Concep 1999:5:102–9.
41. Requena L, Ackerman AB. Hemangioendothelioma? Dermatopathol Pract Concep 1999;5:110–2.
42. Fletcher CDM. The non-neoplastic nature of spindle cell hemangioendothelioma. Am J Clin Pathol
1992;98:545–6.
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Chapter 8 / Benign Neoplasms 191
14. BENIGN LYMPHANGIOENDOTHELIOMA

Benign lymphangioendothelioma is a rare lymphatic neoplasm characterized in a
series of eight patients by Wilson Jones et al. in 1990 (1). Shortly thereafter these authors
coined the name acquired progressive lymphangioma for the same lesion (2). So far, only
37 cases of this uncommon neoplasm have been reported (1–19), under the names acquired
progressive lymphangioma (2–5,9–11,13,14) or benign lymphangioendothelioma
(1,6–,8,12,15,17–19). The lesion described as acquired progressive lymphangioma of
the skin following radiotherapy for breast carcinoma (11) is best interpreted as a benign,
radiation-induced vascular proliferation of the breast (see the next chapter). The lesion
designated as self-healing pseudoangiosarcoma (16) seemingly represents a transient
benign lymphangioendothelioma.
C
LINICAL FEATURES
The lesions of benign lymphangioendothelioma are reddish or bruise-like, slowly
enlarging plaques that lack site predilection (Fig. 37). They can be found on the wrist (1),
face (3,18), scalp (3,18), neck (18), shoulder (1,18), arm (5,6), forearm (1,18), breast
(9,18), back (1,18), abdominal wall (4,16), buttock (14), knee (10), thigh (1,6–8,13,17),
toes (18), sole (18), and oral mucosa (18). Typically, the lesion appears during adolescence
or in young adults as an asymptomatic plaque that increases in size through the years.
With the exception of one patient who had involvement of both forearms (1), and another
Fig. 37. Clinical features of benign lymphangioendothelioma. A plaque with angiomatous appear-
ance involving the anterior thigh of an adult man.
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who presented with two separate lesions involving the face and the arm (3), most patients
have solitary lesions. Lesions have developed in sites previously involved by trauma
(3,17), notably following femoral arteriography (13), and after a tick bite (15). In one
patient, benign lymphangioendothelioma manifested clinically as an actinic keratosis (19).
H
ISTOPATHOLOGIC FEATURES
Benign lymphangioendotheliomas appear histologically as delicate, thin-walled,

endothelium-lined spaces entrapped between collagen bundles (Fig. 38). The appearance
may be confined to the papillary dermis, but it can extend into the reticular dermis and
subcutaneous fat. In superficial areas, the vascular channels are arranged horizontally,
often becoming smaller and more convoluted at deeper levels. The newly formed vessels
may dissect preexisting vessels as well as adnexal structures of the dermis. The vascular
spaces are variably empty or occupied by proteinaceous material. Some vessels show
stromal papillary projections that call to mind papillary endothelial hyperplasia. Eryth-
rocytes and hemosiderin deposits are characteristically absent. Endothelial cells are
present in greater numbers in lesional vessels than in normal lymphatic channels. They
may crowd together but regularly lack nuclear atypia.
Immunohistochemically, the endothelial cells express affinity for Ulex europaeus I
lectin (1,8,14,17), but are unpredictable for factor VIII-related antigen, some cases posi-
tive (8,14,17,18) and others negative (1,7,13). In addition, the endothelial cells may show
immunoreactivity for CD31(17,18), CD34 (8,17,18), HLA-DR (8), smooth muscle actin
(8,18), and ICAM-1 (8). Some studies have demonstrated the presence of type IV col-
lagen (5,14,17) and desmin (5,14) in the matrix that surrounds the vascular channels, thus
creating conjecture that benign lymphangioendothelioma is a complex hamartoma, which
combines blood vessel, lymphatic, and smooth muscle components. Electron micro-
scopic studies have revealed the presence of both tight junctions and well-formed, con-
tinuous basement membranes in the absence of Weibel-Palade bodies (8,13).
Benign lymphangioendothelioma may mimic the patch stage of Kaposi’s sarcoma,
and some authorities (20) have considered the two entities to be indistinguishable. Wilson
Jones et al. (1), in their original series, emphasized that it is sometimes impossible to
make this differentiation in the absence of clinical information. However, the differential
diagnosis can be substantiated by the absence of erythrocytes, hemosiderin deposits, and
plasma cells in lesions of benign lymphangioendothelioma; their presence frequently
characterizes early lesions of Kaposi’s sarcoma. Benign lymphangioendothelioma may
also mimic low-grade angiosarcoma. However, contrastingly, angiosarcoma occurs pre-
dominantly on the face and scalp of elderly patients, and it bears atypical endothelial cells
that form multilayers in less differentiated areas. Extravasated erythrocytes, hemosiderin

deposits, and a mixed or plasma-cell rich inflammatory infiltrate are common features in
angiosarcoma.
T
REATMENT
Some lesions of benign lymphangioendothelioma have resolved spontaneously (7,16).
Surgical excision is generally curative (1,4), but some lesions have persisted after incom-
plete removal. Marked improvement of extensive lesions has been reported following
therapy with oral prednisolone (3), or oral antibiotics (5), namely, ciprofloxacin and
clindamycin, which were given for other reasons (14).
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Chapter 8 / Benign Neoplasms 193
Fig. 38. Histopathologic features of benign lymphangioendothelioma. (A) Irregular slit-like vas-
cular spaces are present involving different levels of the dermis. (B) The vascular spaces appear
empty and are lined by a discontinuous single layer of endothelial cells. A discrete inflammatory
infiltrate of lymphocytes is present in the stroma. (C) Higher magnification demonstrates that
endothelial cells lining the cleft-like vessels show no nuclear atypia.
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References
1. Wilson Jones E, Winkelmann RK, Zachary CB, Reda AM. Benign lymphangioendothelioma. J Am
Acad Dermatol 1990;23:229–35.
2. Wilson Jones E. Malignant vascular tumours. Clin Exp Dermatol 1976;1:287–312.
3. Watanabe M, Kishiyama K, Ohkawara A. Acquired progressive lymphangioma. J Am Acad Dermatol
1983;8:663–7.
4. Tadaki T, Aiba S, Masu S, Tagami H. Acquired progressive lymphangioma as a flat erythematous patch
on the abdominal wall of a child. Arch Dermatol 1988;124:699–701.
5. Zhu WY, Penneys NS, Reyes B, Khatib Z, Schachner L. Acquired progressive lymphangioma. J Am
Acad Dermatol 1991;24:813–5.
6. Chemaly PH, Cricks B, Besseige H, Grossin M, Belaich S. Lymphangio-endotheliome benin. Ann
Dermatol Venereol 1992;119:912–3.

7. Mehregan DR, Mehregan AH, Mehregan DA. Benign lymphangioendothelioma: report of 2 cases.
J Cutan Pathol 1992;19:502–5.
8. Herron GS, Rouse RV, Kosek JC, Smoller BR, Egbert BM. Benign lymphangioendothelioma. J Am
Acad Dermatol 1994;31:362–8.
9. Meunier L, Barneon G, Meynadier J. Acquired progressive lymphangioma. Br J Dermatol 1994;
131:706–8.
10. Soohoo L, Mercurio MG, Brody R, Zaim MT. An acquired vascular lesion in a child. Acquired progres-
sive lymphangioma. Arch Dermatol 1995;131:341–2.
11. Rosso R, Gianelli U, Carnevali L. Acquired progressive lymphangioma of the skin following radio-
therapy for breast carcinoma. J Cutan Pathol 1995;22:164–7.
12. Querol I, Cordoba A, Cisneros MT, Viguri A, Urbiola E. Linfangioendotelioma benigno. Med Cut Iber
Lat Am 1995;23:243–7.
13. Kato H, Kadoya A. Acquired progressive lymphangioma occurring following femoral arteriography.
Clin Exp Dermatol 1996;21:159–62.
14. Grunwald MH, Amichi B, Avinoach I. Acquired progressive lymphangioma. J Am Acad Dermatol
1997;37:656–7.
15. Wilmer A, Kaatz M, Mentzel T, Wollina U. Lymphangioendothelioma after a tick bite. J Am Acad
Dermatol 1998;39:126–8.
16. Bencini PL, Sala F, Valeriani D, et al. Self-healing pseudoangiosarcoma. Unusual vascular proliferation
resembling a vascular malignancy of the skin. Arch Dermatol 1988;124:692–4.
17. Sevila A, Botella Estrada R, Sanmartín O, et al. Benign lymphangioendothelioma of the thigh simulating
a low-grade angiosarcoma. Am J Dermatopathol 2000;22:151–4.
18. Guillou L, Fletcher CD. Benign lymphangioendothelioma (acquired progressive lymphangioma), a
lesion not to be confused with well-differentiated angiosarcoma and patch stage Kaposi’s sarcoma.
Clinicopathologic analysis of a series. Am J Surg Pathol 2000;24:1047–57.
19. Yiannias JA, Winkelmann RK. Benign lymphangioendothelioma manifested clinically as actinic kera-
tosis. Cutis 2001;67:29–30.
20. Sanchez JL, Ackerman AB. Vascular proliferations of the skin and subcutaneous fat. In: Fitzpatrick TB,
Eisen AZ, Wolff K, Freedberg IM, Austen KF, eds. Dermatology in General Medicine, 4th ed., New
York, McGraw-Hill, 1993;1209–43.

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Chapter 8 / Benign Neoplasms 195
15. BENIGN VASCULAR PROLIFERATIONS IN IRRADIATED SKIN
Benign vascular proliferations are well recognized lesions in previously irradiated
areas of the skin. The nomenclature in the literature is complex, compounded by such
terms as lymphangiectases (1), benign lymphangiomatous papules (2), lymphangiomas
(3–13), atypical vascular lesions (14), and benign lymphangioendothelioma (15). These
vascular lesions appear within the field of radiation, and the interval between the application
of radiotherapy and the appearance of the cutaneous lesions spans several years (16).
C
LINICAL FEATURES
The cutaneous lesions include papules, small vesicles, and erythematous plaques
(Fig. 39). Benign appearing lymphangiomatous papules and plaques are the most com-
mon. Confusingly, the term lymphangioma circumscriptum (9,10,12,13) has been applied
by some authors to the localized malformations of lymphatic vessels of the superficial
dermis and as such bears no relation to the lesion under consideration in this chapter (17).
Benign lymphangiomatous papules and plaques are the lymphatic counterpart of telang-
iectases. They result from acquired permanent dilation of lymphatic capillaries that have
appeared in areas of the skin affected by obstruction or destruction of the lymphatics. It
is conjectured that they result from interference in the drainage of lymphatic vessels
secondary to radiotherapy (1–13) or surgery (18). Benign lymphangiomatous papules
and plaques, however, may also appear in the skin of the elderly without any evidence of
primary lymphatic injury (19).
H
ISTOPATHOLOGIC FEATURES
Under low magnification, the lesions appear as relatively well-circumscribed capil-
lary proliferations centered in the dermis, without extension into the subcutaneous fat.
The epidermis is usually spared (Fig. 40). Most lesions show irregularly dilated lym-
phatic spaces that branch and anastomose within the superficial dermis. The vascular
spaces, devoid of content, are lined by a discontinuous single layer of endothelial cells

with flattened nuclei. Commonly, adjacent vascular channels lie “back-to-back,” sepa-
rated only by a thin layer of endothelial cells. Multiple papillary projections, covered by
a single layer of endothelium, project into the lumina of the dilated lymphatic. The stroma
Fig. 39. Clinical features of a benign vascular proliferation in irradiated skin. This patient with
breast carcinoma was treated with mastectomy and subsequent radiotherapy. In addition to the
abundant telangiectases secondary to radiodermatitis, there are scattered small papules with an
angiomatous appearance.
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196 Sangüeza and Requena / Pathology of Vascular Skin Lesions
consists of fibrillary collagen rich with spindle, or stellate, fibroblasts. Nodular infiltrates
of lymphocytes with germinal centers are occasionally present in the vicinity of the
dilated vascular channels. Rarely, vascular proliferations are poorly circumscribed and
focally intermingled with irregular jagged vascular spaces that may permeate the entire
dermis. Endothelial cells line the latter inconspicuously. Irregular slit-like vascular spaces
may be seen between collagen bundles of the dermis, together with tufts of endothelial
cells that protrude into the lumina of the newly formed vessels (16).
The endothelial cells that line the vascular spaces express immunoreactivity for CD31, but
they do so only focally or not at all for CD34. Although a minority of newly formed vessels
show an attenuated muscle layer, external to the endothelial cells, which has on occasion
immunoreactivity for α-smooth muscle actin antibody, this marker is usually nonreactive.
Reactivity for Ki-67 is negative among the endothelial cell nuclei (16). The immunohis-
tochemical profile substantiates the lymphatic nature of these newly formed vessels.
Some dermal vascular responses to irradiation, such as the benign lymphangio-
endothelioma (15) or an atypical angiomatous proliferation (14), may mimic the histo-
pathologic appearance of the patch stage of Kaposi’s sarcoma or even a well-differentiated
angiosarcoma. In contrast to the patch stage of Kaposi’s sarcoma, atypical benign vas-
Fig. 40. Histopathologic features of benign vascular proliferation in irradiated skin. (A) Low
power shows dilated vascular spaces at different levels of the dermis. (B) These vessels show a
lymphatic appearance, with thin walls and a single and discontinuous layer of endothelial cells
lining their lumina. In some vessels there are small intraluminal papillary projections of endothe-

lial cells.
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Chapter 8 / Benign Neoplasms 197
cular proliferations, as induced by radiation, do not contain erythrocytes or hemosiderin
deposits, or stromal plasma cells. The striking tufts of endothelial cells and the intravas-
cular papillary projections, evidenced in the vascular proliferations of irradiated skin, are
absent in the lesions of Kaposi’s sarcoma. In contrast to well-differentiated angiosar-
coma, atypical dermal vascular proliferations in irradiated skin do not involve the sub-
cutaneous tissues. Distinctively, they have no cytologic atypia. The nuclei of the
endothelial cells are monomorphous, have inconspicuous nucleoli, and lack mitotic fig-
ures. In contrast, the endothelial cells of an angiosarcoma may form stratified layers that
irregularly line anastomostic channels, to a degree not seen in the atypical vascular
proliferations of irradiated skin.
T
REATMENT
The vascular proliferations in irradiated skin do not call for therapy, and the accounts
in the literature have not provided examples of metastasis.
References
1. Ambrojo P, Fernández-Cogolludo E, Aguilar A, et al. Cutaneous lymphangiectases after therapy for
carcinoma of the cervix: a case with unusual clinical and histological features. Clin Exp Dermatol
1990;15:57–9.
2. Díaz-Cascajo C, Borghi S, Weyers W, Retzlaff H, Requena L, Metze D. Benign lymphangiomatous
papules of the skin following radiotherapy. A report of five new cases and review of the literature.
Histopathology 1999;35:319–27.
3. Fisher I, Orkin M. Acquired lymphangioma (lymphangiectasis). Arch Dermatol 1970;101:230–4.
4. Gianelli V, Rockley PF. Acquired lymphangiectases following mastectomy and radiation therapy.
Report of a case and review of the literature. Cutis 1996;58:276–8.
5. Handfield-Jones SE, Prendville WJ, Norman S. Vulval lymphangiectasia. Genitourin Med 1989;
65:335–7.
6. Harwood CA, Mortimer PS. Acquired vulvar lymphangiomata mimicking genital warts. Br J Dermatol

1993;129:334–6.
7. Kennedy CTC. Lymphangiectasia of the vulva following hysterectomy and radiotherapy. Br J Dermatol
1990;123 (suppl. 37):92–3.
8. Kurwa A, Waddinton E. Post mastectomy lymphangiomatosis. Br J Dermatol 1968;80:840.
9. LaPolla J, Foucar E, Leshin B et al. Vulvar lymphangioma circumscriptum: a rare complication of
therapy for squamous cell carcinoma of the cervix. Gynecol Oncol 1985;22:363–6.
10. Leshin B, Whitaker D, Foucar E. Lymphangioma circumscriptum following mastectomy and radiation
therapy. J Am Acad Dermatol 1986;15:1117–9.
11. Plotnick H, Richfield D. Tuberous lymphangiectatic varices secondary to radical mastectomy. Arch
Dermatol Syphilol 1956;74:466–8.
12. Prioleau PG, Santa Cruz DJ. Lymphangioma circumscriptum following radical mastectomy and radia-
tion therapy. Cancer 1978;42:1989–91.
13. Young AW Jr, Wind RM, Tovell HM. Lymphangioma of vulva: acquired following treatment for
cervical cancer. NY State J Med 1980;80:987–9.
14. Finenberg S, Rosen PP. Cutaneous angiosarcoma and atypical vascular lesions of the skin and breast
after radiation therapy for breast carcinoma. Am J Clin Pathol 1994;102:757–63.
15. Rosso R, Gianelli U, Carnevali L. Acquired progressive lymphangioma of the skin following radio-
therapy for breast carcinoma. J Cutan Pathol 1995;22:164–7.
16. Requena L, Kutzner H, Mentzel T, Durán R, Rodríguez-Peralto JL. Benign vascular proliferations in
irradiated skin. Am J Surg Pathol 2002;26:328–37.
17. Requena L, Sangueza OP. Cutaneous vascular anomalies. Part I. Hamartomas, malformations, and
dilatation of preexisting vessels. J Am Acad Dermatol 1997;37:523–9.
18. Ziv R, Schewach-Millet M, Trau H. Lymphangiectasia: a complication of thoracotomy for bronchial
carcinoid. Int J Dermatol 1988;27:123.
19. Cecchi R, Bartoli L, Brunetti L, Pavesi M, Giomi A. Lymphangioma circumscriptum of the vulva of late
onset. Acta Derm Venereol 1995;75:79–93.
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16. GLOMUS TUMORS
Glomus tumors are uncommon neoplasms that arise from modified smooth muscle

cells normally present in specialized arteriovenous shunts in acral sites, mainly the fin-
gertips. These anatomic structures, known as the Sucquet-Hoyer canals, contribute to
temperature regulation. Sucquet-Hoyer canals are lined by endothelial cells and possess
several intramural layers of glomus cells. The vascular channel connects an afferent
arteriole to an efferent venule (1). Glomus tumors are considered to originate from the
glomus cells; thus they occur preferentially in acral areas (2).However, “renegade” or
“ectopic” glomus tumors have been described in extracutaneous sites notably in the bone
(3), stomach (4), colon (5), trachea (6), and mediastinum (7). Since glomus bodies are
sparse, or presumptively absent in these areas, conceptually glomus tumors may arise from
either ectopic glomus cells or from undifferentiated perivascular cells (8).
C
LINICAL FEATURES
Two types of glomus tumors have been described, solitary and multiple. They do not
fully share distribution, clinical characteristics, or histopathologic features (9). The soli-
tary glomus tumor is more common. It creates a small, purple nodule preferentially in
acral areas of the extremities, especially nail beds of the fingers (Fig. 41) and toes (2).
Subungual lesions may create a blue-red flush and with time may erode the distal phalanx
(10,11). There is a striking predominance among female patients (10). The lesion fre-
quently creates severe paroxysmal pain, usually precipitated by exposure to cold or minor
pressure. The cause of the pain is a subject of conjecture. However, the recently demon-
strated substance P in nerve fibers of glomus tumors incriminates this substance, since
it is known to be a primary sensory afferent neurotransmitter for mediating painful stimuli
(12). Solitary glomus tumors may on occasion occur in aberrant locations. They typically
appear in the early adult years, although not always. In general, they affect both sexes,
although there is a female predominance (10,11).
Multiple glomus tumors are much less common than their solitary counterpart. They
are termed glomangiomas descriptively in accordance with their angiomatous appearance.
In contrast to the solitary glomus lesion, glomangiomas present during childhood as small
bluish nodules situated deep in the dermis and widely scattered in the skin (Fig. 42).
Multiple lesions have been noted to aggregate in an anatomic region (13–18). Gloman-

giomas are rarely subungual. They are less commonly painful. Noteably, multiple glo-
mangiomas are often inherited in an autosomal dominant manner (9,19–25). The gene is
located in chromosome 1p21-22 (26). Presumably, sporadic cases occur from somatic
mutation of the same gene. Glomangiomas are often sufficiently large to be raised, soft,
and compressible. As such they can be mistaken for lesions of the blue rubber bleb nevus
syndrome, even in the absence of intestinal bleeding (27). Patients may develop Kasabach-
Merritt syndrome (28). Occasionally, glomangiomas present as a solitary telangiectatic
plaque-like lesion (29) (Fig. 43). Mounayer et al. (30) recently reported seven patients
with multiple large facial plaque-like glomangiomas that mimicked common facial
venous malformations (Fig. 44). These extensive facial glomangiomas were not painful.
Unlike facial venous malformations, the large facial glomangiomas described by
Mounayer et al. (30) were distinctly nodular, deep blue or purple, and poorly compress-
ible. Histopathologic study disclosed one or several rows of glomus cells present in the
walls of the large tortuous venous channels.
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Chapter 8 / Benign Neoplasms 199
Glomangiomyomas consist of tumors composed of neoplastic cells that show a gradual
transition from glomus cells to elongated, mature smooth muscle cells (Fig. 45).
H
ISTOPATHOLOGIC FEATURES
Histopathologically, solitary glomus tumors are customarily solid, well-circumscribed
nodules surrounded by compressed fibrous tissue. The neoplasm is cytologically formed
of clusters of round or polygonal monomorphous glomus cells with large, round, plump
Fig. 41. Clinical features of subungual glomus tumor. A purple nodule is seen under the nail plate.
Fig. 42. Clinical features of multiple glomus tumors. Multiple small blue nodules scattered on the
back of an adult woman.
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nuclei and scant eosinophilic cytoplasm (Fig. 46). Endothelium-lined vascular spaces
create a core in the center of some of these clusters. The uniformity of the neoplastic cells

and their lack of pleomorphism are characteristic attributes of glomus tumors. Some
lesions acquire a mucinous stroma (2). Abundant nerve fibers (10) and mast cells (31) are
seen in some solitary glomus tumors. Rare histopathologic variants include (1) lesions
with large, hyperchromatic nuclei that probably represent a degenerative phenomenon
(32); (2) glomus tumors composed of glomus cells with abundant granular cytoplasm,
Fig. 43. Rare variant of solitary glomangioma with the appearance of a telangiectatic plaque.
Histopathologic study demonstrated conventional features of glomangioma.
Fig. 44. Large facial glomangioma mimicking a common facial venous malformation.
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Chapter 8 / Benign Neoplasms 201
which have been termed “oncocytic” glomus tumors (9,33,34); (3) intravascular glomus
tumors (35,36); (4) intraneural glomus tumors (8,37); (5) epithelioid glomus tumor (38);
and (6) infiltrating glomus tumors (39,40). The lesions termed glomangiomyomas con-
sist of glomus tumors in which there is an admixture of glomus cells and elongated,
mature smooth muscle cells (32) (Fig. 47) .
Histopathologically, glomangiomas are less well-circumscribed lesions than solitary
glomus tumors. Some are made up of several nodules within the dermis. Some have an
appearance that calls to mind a hemangioma (Fig. 48). These are composed of irregular
dilated endothelium-lined vascular channels that contain red blood cells and, distinc-
tively, have small intramural aggregations of glomus cells. Glomus cells may form cords
or small clusters in adjacent stroma, but numerically they are sparse relative to their
numbers in a solitary glomus tumor. As stated, some lesions can be difficult to distinguish
from a conventional hemangioma; this is particularly true when thrombosis and phlebo-
lith formation occurs within the vascular channels of a glomangioma (Fig. 49).
Glomus cells were once considered pericytes (31). However, ultrastructural studies
have demonstrated that the cells of the normal glomus, as well as the neoplastic cells of
both the solitary and the multiple glomus tumors, contain pinocytotic vesicles and are
surrounded by a basal lamina. Abundant numbers of myofilaments condense focally to
form dense bodies within the cytoplasm, in testimony to the cell’s nature as a modified
smooth muscle cell (2,9,20,22,31,40–48).

Immunohistochemically, glomus cells express vimentin, muscle-specific actin, and
α-smooth muscle actin (36,49–55). Desmin positivity has been described by some authors
Fig. 45. Clinical features of glomangiomyoma. An exophytic and pedunculated lesion with an
angiomatous appearance on the back of an adult woman.
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(51,52,56), but this finding has been not corroborated by others (36,48,53). Laminin and
type IV collagen outline the glomus cells (51). Highly cellular glomus tumors can be
mistaken for solid apocrine hidradenomas (50). However, immunohistochemistry resolves
this histopathologic dilemma since apocrine hidradenomas express immunoreactivity for
cytokeratins and carcinoembryonic antigen, whereas glomus tumors do not (50).
T
REATMENT
The cure for solitary glomus tumors is simple excision. In patients with multiple
lesions, excision should be restricted to painful lesions. Successful treatment of multiple
glomangiomas has been reported with electron beam irradiation (57) and laser therapy
(58–61). Although glomus tumors are benign neoplasms, very rare examples of
glomangiosarcomas have arisen in the setting of a benign glomus tumor in patients with
multiple glomangiomas (62).
References
1. Masson P. Le glomus neuromyo-arteriel des régions tactil et ses tumeurs. Lyon Chir 1924:21:257–80.
2. Tsuneyoshi M, Enjoji M. Glomus tumor: a clinicopathologic and electron microscopic study. Cancer
1982;50:1601–7.
Fig. 46. Histopathologic features of subungual glomus tumor. (A) Scanning power shows a mostly
solid cellular proliferation. (B) Higher magnification shows that the lesion is composed of clusters
of round monomorphous cells. (C) Still higher magnification demonstrates that neoplastic
cells have large round or plump nuclei and scant eosinophilic cytoplasm, all characteristics of
glomus cells.
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Chapter 8 / Benign Neoplasms 203

3. Kobayashi Y, Kawaguchi T, Imoto K, et al. Intraosseous glomus tumor in the sacrum: a case report. Acta
Pathol Jpn 1990;40:856–9.
4. Kanwar YS, Manaligod JR. Glomus tumor of the stomach: an ultrastructural study. Arch Pathol
1975;99:392–7.
5. Barua R. Glomus tumor of the colon: first reported case. Dis Colon Rectum 1988;31:138–40.
6. Kim YI, Kim JH, Suh JS, et al. Glomus tumor of the trachea: report of a case with ultrastructural
observations. Cancer 1989;64:881–6.
7. Brindley GV. Glomus tumor of the mediastinum. J Thorac Surg 1949;18:417–20.
8. Calonje E, Fletcher CDM. Cutaneous intraneural glomus tumor. Am J Dermatopathol 1995;17:395–8.
9. Pepper MC, Laubenheiner R, Cripps DJ. Multiple glomus tumors. J Cutan Pathol 1977;4:244–57.
10. Stout AP. Tumors of the neuromyoarterial glomus. Am J Cancer 1935;24:255–72.
11. Shugart RR, Soule EH, Johnson EW Jr. Glomus tumor. Surg Gynecol Obstet 1963;117:334–40.
12. Kishimoto S, Nagatani H, Miyashita A, Kobayashi K. Immunohistochemical demonstration of sub-
stance P-containing nerve fibers in glomus tumors. Br J Dermatol 1985;113:213–8.
13. Laymon CW, Paterson WC. Glomangioma (glomus tumor): a clinico-pathologic study with special
reference to multiple lesions appearing during pregnancy. Arch Dermatol 1965;92:509–13.
14. Landthaler M, Braun-Falco O, Ecklert F, Stolz W, Dorn M. Wolf HH. Congenital multiple plaque-like
glomus tumor. Arch Dermatol 1990;126:1203–7.
15. Gorlin RJ, Fusaro RM, Benton JW. Multiple glomus tumor of pseudocavernous hemangioma type.
Report of a case manifesting a dominant inheritance pattern. Arch Dermatol 1960;82:776–8.
16. Yoon T-Y, Lee H-T, Chang S-H. Giant congenital multiple patch-like glomus tumors. J Am Acad
Dermatol 1999;40:826–8.
Fig. 47. Histopathologic features of glomangiomyoma. (A) Low power shows dense cellular
proliferations involving the entire thickness of the dermis. (B) Neoplastic cells show intermediate
characteristics between glomus cells and mature smooth muscle cells. (C) Cellular aggregates are
mostly solid, with inconspicuous vascular lumina.
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Chapter 8 / Benign Neoplasms 205

Fig. 48. ( Opposite page) Histopathologic features of glomangioma. (A) Low power shows cellular
aggregates and dilated vascular structures at different levels of the dermis. (B) Higher magnifica-
tion demonstrates that the vascular channels are surrounded by round monomorphous cells. (C)
Still higher magnification demonstrates that the cells surrounding the vascular channels show
characteristics of glomus cells.
Fig. 49. Histopathologic features of large facial glomangioma mimicking a common facial venous
malformation. (A) Low power shows dilated vascular channels involving different levels of the
dermis. (B) Higher magnification demonstrates that these dilated vascular channels are surrounded
by clusters of glomus cells.
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206 Sangüeza and Requena / Pathology of Vascular Skin Lesions
17. Yang J-S, Ko J-W, Suh K-S, Kim S-T. Congenital multiple plaque-like glomangiomyoma. Am J
Dermatopathol 1999;21:454–7.
18. Carvalho VO, Taniguchi K, Giraldi S, et al. Congenital plaquelike glomus tumor in a child. Pediatr
Dermatol 2001;18:223–6.
19. Hatchome N, Kado T, Tagami H. Numerous papular glomus tumors localized on the abdomen. Acta
Derm Venerol (Stockh) 1986;66:161–4.
20. Rycroft RJG, Menter MA, Sharvill DE, et al. Hereditary multiple glomus tumors. Trans St John’s Hosp
Derm Soc 1975;61:70–81.
21. Conant M, Wiesenfeld S. Multiple glomus tumors of the skin. Arch Dermatol 1971;103:481–7.
22. Goodman TF, Abele DC. Multiple glomus tumors. Arch Dermatol 1971;103:11–23.
23. Taafe A, Barker D, Wyat EH, Bury HPR. Glomus tumors: a clinicopathological survey. Clin Exp
Dermatol 1980;5:219–25.
24. Requena L, Requena C, Sánchez M, et al. Glomangiomas multiples hereditarios. Actas Dermosifiliogr
1987;78:245–7.
25. Blume-Peytavi U, Adler YL, Geilen CC, et al. Multiple familial cutaneous glomangioma: a pedigree of
4 generations and critical analysis of histologic and genomic differences of glomus tumors. J Am Acad
Dermatol 2000;42:633–9.
26. Boon LM, Brouillard P, Irrthum A, et al. A gene for inherited cutaneous venous anomalies (“gloman-
giomas”) localized to chromosome 1p21-22. Am J Hum Genet 1999;65:125–33.

27. Mukhtar JAK, Pfeger L. Angiomatosis cutis disseminata (Beziehungenzum Blue Rubber Bleb Nevus).
Hautarzt 1964;15:230–5.
28. McEvoy BF, Waldman PM, Tye MJ. Multiple hamartomatous glomus tumors of the skin. Arch Dermatol
1971;104:188–91.
29. Requena L, Galvan C, Sánchez Yus E, Sangueza O, Kutzner H, Furio V. Solitary plaque-like telangiec-
tatic glomangioma. Br J Dermatol 1998;139:902–5.
30. Mounayer C, Wassef M, Enjolras O, Boukobza M, Mulliken J. Facial “glomangiomas”: large facial
venous malformations with glomus cells. J Am Acad Dermatol 2001;45:239–45.
31. Murad TM, von Haam E, Murthy MSN. Ultrastructure of a hemangiopericytoma and a glomus tumor.
Cancer 1968;22:1239–49.
32. Enzinger FM, Weiss SW. Soft Tissue Tumors. 3rd ed., St. Louis, Mosby, 1995:701–83.
33. Slater DN, Cotton DWK, Azzopardi JG. Oncocytic glomus tumour: a new variant. Histopathology
1987;11:523–31.
34. Shin DLH, Park SS, Lee JH, et al. Oncocytic glomus tumor of the trachea. Chest 1990;98:1021–3.
35. Beham A, Fletcher CDM. Intravenous glomus tumor: a previously undescribed phenomenon. Virchows
Arch Pathol Anat 1991;418:175–7.
36. Googe PB, Griffin WC. Intravenous glomus tumor of the forearm. J Cutan Pathol 1993;20:359–63.
37. Kline SC, Russell Moore J, de Mente SH. Glomus tumor originating within a digital nerve. J Hand Surg
1990;15A:98–101.
38. Pulitzer DR, Martin PC, Reed RJ. Epithelioid glomus tumor. Hum Pathol 1995; 26:1022–7.
39. Gould EW, Manivel JC, Albores-Saavedra J, Monforte H. Locally infiltrative glomus tumors and
glomangiosarcomas: a clinical ultrastructural and immunohistochemical study. Cancer 1990;65:310–8.
40. Skelton HG, Smith KJ. Infiltrative glomus tumor arising from a benign glomus tumor: a distinctive
immunohistochemical pattern in the infiltrative component. Am J Dermatopathol 1999;21:562–6.
41. Tarnowski WM, Hashimato K. Multiple glomus tumors: an ultrastructural study. J Invest Dermatol
1969;52:474–8.
42. Venkatachalam MA, Greally JG. Fine structure of glomus tumor: similarity of glomus cells to smooth
muscle. Cancer 1969;23:1176–84.
43. Goodman TF. Fine structure of the cells of the Sucquet-Hoyer canal. J Invest Dermatol 1972;59:363–9.
44. Luders G, Schlote W, Reinhard M. Zur Ultrastruktur von Glomustumorem und Glomusorganen. Arch

Klin Exp Dermatol 1970;238:398–416.
45. Toker C. Glomangioma: an ultrastructural study. Cancer 1969;23:487–92.
46. Murata Y, Tsuji M, Tani M. Ultrastructure of multiple glomus tumor. J Cutan Pathol 1984;11:53–8.
47. Harris M. Ultrastructure of a glomus tumor. J Clin Pathol 1971;24:520–3.
48. Miettinem M, Lehto V-P, Virtanen I. Glomus tumor cells evaluation of smooth muscle and endothelial
cell properties. Virchows Arch (B) 1983;43:139–49.
49. Hague S, Modlin IM, West AB. Multiple glomus tumors of the stomach with intravascular spread. Am
J Surg Pathol 1992;16:291–9.
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Chapter 8 / Benign Neoplasms 207
50. Haupt HM, Stern JB, Berlin SJ. Immunohistochemistry in the differential diagnosis of nodular hidrad-
enoma and glomus tumor. Am J Dermatopathol 1992;14:310–4.
51. Nuovo MA, Grimes MM, Knowless DM. Glomus tumors: clinicopathologic and immunohistochemical
analysis of forty cases. Surg Pathol 1990;3:31–40.
52. Porter PG, Bigler SA, McNutt NS, et al. The immunophenotype of hemangiopericytoma and glomus
tumors with special reference to muscle protein expression: an immunohistochemical study and review
of the literature. Mod Pathol 1991;4:46–52.
53. Schurch W, Skalli O, Lagace R, et al. Intermediate filament proteins and actin isoforms as markers for
soft tissue tumor differentiation and origin. III. Hemangiopericytomas and glomus tumors. Am J Pathol
1990;136:771–86.
54. Kaye VM, Dehner LP. Cutaneous glomus tumor: a comparative immunohistochemical study with
pseudoangiomatous intradermal melanocytic nevi. Am J Dermatopathol 1991;13:2–6.
55. Dervan PA, Tobbia IN, Casey M, et al. Glomus tumours: an immunohistochemical profile of 11 cases.
Histopathology 1989:14:483–91.
56. Brooks IJ, Miettinen M, Virtanen J. Desmin immunoreactivity in glomus tumors. Am J Clin Pathol
1987;87:292.
57. Nishimoto K, Nishimoto M, Yamamoto S, Nakagawa T, Takaiwa T, Tanabe M. Multiple glomus
tumours: successful treatment with electron beam irradiation. Br J Dermatol 1990;123:657–61.
58. Goldman L. Laser treatment of multiple progressive glomangiomas. Arch Dermatol 1978;114:1853–4.
59. Goldman L. Laser treatment of multiple glomangiomas: progress report of 13 yr after treatment. Arch

Dermatol 1981;117:451–2.
60. Barnes L, Estes SA. Laser treatment of hereditary multiple glomus tumors. J Dermatol Surg Oncol
1986;12:912–5.
61. Sharma JK, Miller R. Treatment of multiple glomangioma with tuneable dye laser. J Cutan Med Surg
1999;3:167–8.
62. Brathwaite CD, Poppiti RJ. Malignant glomus tumor: a case report of widespread metastases in a patient
with multiple glomus body hamartomas. Am J Surg Pathol 1996;20:233–8.
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17. HEMANGIOPERICYTOMA
Since Stout and Murray’s initial description of hemangiopericytoma in 1942 (1), this
entity has been a controversial subject. The controversy is fueled by the uncertainty of
the cell of origin, wherein pericytes are indistinguishable by light microscopy from
endothelial cells and fibroblasts. In addition, there are no established histopathologic
criteria to differentiate the benign and malignant forms of hemangiopericytoma. Since
several soft tissue neoplasms share histopathologic features with hemangiopericytoma,
many authors consider this neoplasm to be merely a histopathologic pattern rather than
a distinctive entity. However, currently it is generally accepted that hemangiopericytomas
create a histopathologic pattern of a specific entity. A critical review on this subject has
been published recently (2).
Hemangiopericytomas are most commonly found within the soft tissues of the
extremities, especially those of the thigh, pelvic fossa, and retroperitoneum. Although
they rarely affect the skin, cutaneous and subcutaneous forms of hemangiopericytoma
have been reported (3–7).
C
LINICAL FEATURES
Although the lesion usually presents as a solitary firm nodule on an extremity (Fig. 50),
multiplicity of lesions have been encountered (8,9).
H
ISTOPATHOLOGIC FEATURES

Enzinger and Smith (10) distinguish two types of hemangiopericytomas: adult and
congenital, or infantile types. These variants differ both clinically and histopathologi-
cally (10). The adult variant of hemangiopericytoma is more common and usually appears
as a single nodule in the soft tissue of a limb (10–12). Histopathologically, it is charac-
terized by compact cellular areas that embody endothelium-lined, branching vessels.
Individual cells show round to oval nuclei and cytoplasm with ill-defined borders. The
Fig. 50. Clinical features of hemangiopericytoma. An erythematous nodule on the knee of an
adult man.
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Chapter 8 / Benign Neoplasms 209
vascular channels form a continuous network distinguished by the presence of a “stag
horn” or “antler-like” configuration (5) (Fig. 51). The stroma may be myxoid or fibrotic,
with rare foci of cartilaginous and osseus metaplasia (10). Although the benign and
malignant forms of hemangiopericytoma may be very difficult to distinguish one from
the other, prominent mitotic activity, necrosis, hemorrhage, increased cellularity, and
large gross size are the most frequent indices of metastatic potential (10). The congenital
form of hemangiopericytoma originates almost exclusively in the subcutis, as a
multilobulated (10) and sometimes multicentric lesion (13,14). Although the congenital
and infantile forms of hemangiopericytoma possess the characteristic cellular morphol-
ogy and anastomotic vascular configurations of the adult form, they are multilobulated
neoplasms. Distinctively, even though mitotic figures and necrosis may be present, the
lesions invariably follow a benign course (10,13,15). Mentzel et al. (16) have recently
proposed that infantile hemangiopericytoma and infantile myofibromatosis are a spectra
of a single entity.
Immunohistochemically, the neoplastic cells of a hemangiopericytoma express reac-
tivity for vimentin, factor XIIIa, HLA-DR, CD34, and CD57 (17–20), but they do not
Fig. 51. Histopathologic features of hemangiopericytoma. (A) Scanning power shows a well-
circumscribed lesion containing numerous irregular dilated vascular structures. (B) Irregular
branching endothelium-lined vascular channels are surrounded by tightly packed cellular areas.
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210 Sangüeza and Requena / Pathology of Vascular Skin Lesions
stain for factor VIII-related antigens, Ulex europaeus I lectin, α-smooth muscle actin,
desmin, myoglobin, cytokeratin, and epithelial membrane antigen (19–23). Ultrastruc-
tural studies have demonstrated that the neoplastic cells simulate normal pericytes, since
they have large round nuclei, pale cytoplasm with few organelles, numerous elongated
extensions, abundant numbers of pinocytotic/vesicles, and a basal lamina that surrounds
each individual cell (9,24–29). In addition to the appearance of classic pericytes, other
cells have intermediate morphologies between pericytes and smooth muscle cells. They
contain dense bodies, bundles of microfilaments, and attachment plates (9,24,26–28).
T
REATMENT
In view of the marginal histologic criteria for assessment of biologic behavior among
hemangiopericytomas, complete surgical excision is desirable. Radiotherapy has been
ineffectual (30).
References
1. Stout AP, Murray MR. Hemangiopericytoma: a vascular tumor featuring Zimmerman’s pericytes. Ann
Surg 1942;116:26–33.
2. Nappi O, Ritter JH, Pettinato G, Wick MR. Hemangiopericytoma: histopathological pattern or clinico-
pathological entity. Semin Diagn Pathol 1995; 12:221–32.
3. Cole HN Jr, Reagan JW, Lund HZ. Hemangiopericytoma. Arch Dermatol 1955;72:328–34.
4. Sims CF, Kirsch N, MacDonald RG. Hemangiopericytoma. Arch Dermatol Syph 1948;58:194–205.
5. Bianchi O, Abulafia J, Mirande L. Hémangiopericytoma cutané. Ann Dermatol Syph 1968;95:269–84.
6. Reich H. Das Hamangiopericytom. Hautarzt 1973;24:275–85.
7. Schneider W, Undeutsch W. Seltene Blutgefassgeschwulste der Haut. Hautarzt 1967;18:437–45.
8. Saunders TS, Fitzpatrick TB. Multiple hemangiopericytomas: their distinction from glomangiomas
(glomus tumor). Arch Dermatol 1957;76:731–4.
9. Kuhn C III, Rosai J. Tumors arising from pericytes: ultrastructure and organ culture of a case. Arch
Pathol 1969;88:653–63.
10. Enzinger FM, Smith BH. Hemangiopericytoma: an analysis of 106 cases. Hum Pathol 1976;7:61–82.
11. McMaster MJ, Soule EH, Ivins JC. Hemangiopericytoma: a clinicopathologic study and long-term

follow-up of 60 patients. Cancer 1976;36:2232–44.
12. Argenvall L, Kindblom L-G, Nielsen JM, et al. Hemangiopericytoma: a clinicopathologic, angiographic
and microangiographic study. Cancer 1978;42:2412–27.
13. Kauffman SL, Stout AP. Hemangiopericytoma in children. Cancer 1960;13:695–710.
14. Hayes MM, Dietrich BE, Uys CJ. Congenital hemangiopericytomas of skin. Am J Dermatopathol
1986;8:148–53.
15. Altmeyer P, Nodl F. Das Hamangioperizytom des Sanglings. Hautarzt 1976;27:272–6.
16. Mentzel T, Calonje E, Nascimiento AG, Fletcher CDM. Infantile hemangiopericytoma versus infantile
myofibromatosis: study of a series suggesting a continuous spectrum of infantile myofibroblastic lesions.
Am J Surg Pathol 1994;18:922–30.
17. Nemes Z. Differentiation markers in hemangiopericytoma. Cancer 1992;69:133–40.
18. Aziza J, Mazerolles C, Selves J, et al. Comparison of the reactivities of monoclonal antibodies QBEND10
(CD34) and BNH9 in vascular tumors. Appl Immunohistochem 1993;1:51–60.
19. Traweek ST, Kandalaft PL, Mehta P, et al. The human hematopoietic progenitor cell antigen (CD34) in
vascular neoplasia. Am J Clin Pathol 1991;96:25–31.
20. D’Amore E, Manivel JC, Sung JH. Soft tissue and meningeal hemangiopericytomas: an immunohis-
tochemical and ultrastructural study. Hum Pathol 1990;21:414–23.
21. Porter PG, Bigler SA, McNutt NS, et al. The immunophenotype of hemangiopericytoma and glomus
tumors with special reference to muscle protein expression: an immunohistochemical study and review
of the literature. Mod Pathol 1991;4:46–52.
22. Schurch W, Skalli O, Lagace R, et al. Intermediate filament proteins and actin isoforms as markers for
soft tissue tumor differentiation and origin. III. Hemangiopericytomas and glomus tumors. Am J Pathol
1990;136:771–86.
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Chapter 8 / Benign Neoplasms 211
23. Miettinen M, Holthofer H, Lehto VP, et al. Ulex europaeus I lectin as a marker for tumors derived from
endothelial cells. Am J Clin Pathol 1983;79:32–6.
24. Murad TM, von Haam E, Murthy MSN. Ultrastructure of a hemangiopericytoma and a glomus tumor.
Cancer 1968;22:1239–49.
25. Battifora H. Hemangiopericytoma: ultrastructural study of five cases. Cancer 1973;31:1418–32.

26. Nunnery EW, Kahn LB, Reddick RL, et al. Hemangiopericytoma: a light microscopic and ultrastructural
study. Cancer 1981;47:906–13.
27. Hahn MJ, Dawson R, Esterly JA, et al. Hemangiopericytoma: an ultrastructural study. Cancer
1973;31:255–61.
28. Dardick I, Hammar SP, Scheithauer BW. Ultrastructural spectrum of hemangiopericytoma: a compara-
tive study of fetal, adult and neoplastic pericytes. Ultrastruct Pathol 1989;13:111–34.
29. Ramsey HJ. Fine structures of hemangiopericytoma and hemangioendothelioma. Cancer 1966;
19:2005–18.
30. O’Brien P, Basfiled RD. Hemangiopericytoma. Cancer 1965;18:249–52.
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18. CUTANEOUS MYOFIBROMA
In 1981, Chung and Enzinger (1) proposed the term infantile myofibromatosis for a
clinicopathologic entity with myofibroblastic differentiation. They recognized solitary
and multicentric forms, the former being the more common. Although most of their
lesions occurred in children, these authors also acknowledged occasional cases of
myofibromatosis in adults and (1), subsequent reports have reaffirmed this observation.
Paradoxically, the solitary type of myofibroma occurs more commonly in adults with
lesions located preferentially in the dermis (2–15). Terms such as cutaneous myofibroma
(3) and solitary myofibroma (4,5) have been most appropriately used to describe this
distinctive lesion.
Infantile myofibromatosis usually presents before the age of 2 years. In addition to the
skin, these lesions may involve deeper structures such as muscle and bone. Although
most lesions are disposed to spontaneous regression, visceral involvement is predisposed
to fatality. Contrastingly, the lesions of adult myofibroma are solitary, appear during
adult life, show no tendency to regress, affect only the dermis and subcutaneous tissue,
and manifest an entirely benign biologic behavior.
C
LINICAL FEATURES
Clinically, adult cutaneous myofibroma appears as a solitary cutaneous or subcutane-

ous nodule, firm in consistency, and lacking specific clinical features that allow a definite
diagnosis prior to biopsy. Both genders are affected with equal frequency, the distal
portions of the upper and lower extremities (Fig. 52) being the most commonly targeted
(12). The lesions may be painful (12).
H
ISTOPATHOLOGIC FEATURES
Among cutaneous adult myofibromas, the histologic appearance varies with the
duration of the lesion (12). Earlier lesions feature the vascular component. In this vascu-
lar type of cutaneous adult myofibroma, variable numbers of endothelium-lined vascular
Fig. 52. Cutaneous myofibroma involving the inner aspect of the foot.
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Chapter 8 / Benign Neoplasms 213
spaces branch irregularly and closely resemble hemangiopericytoma. In addition, there
are sheets of monomorphic, round to polygonal cells with a glomus-like appearance.
Most cases intermingle the hemangiopericytoma-like areas with the glomus-like cells;
however sometimes the primitive pericyte-like cells surround only the anastomosing
endothelium-lined hemangiopericytoma-like areas. The stroma consists of sclerotic
collagenous bundles intermingled with whorls of smooth muscle-like cells and focal
calcification. Some tumors show a polypoid growth into the vascular spaces, and these
vascular plugs may create the false appearance of vascular invasion.
Mature lesions show either a nodular or a multinodular pattern. The nodular or cellular
type of adult cutaneous myofibroma is characteristically a sharply circumscribed but
nonencapsulated, single intradermal nodule, composed of solid aggregations of plump
spindle cells with myofibroblastic appearances. In some areas, the neoplastic cells assume
perivascular arrangements and show transitions with the smooth muscle cells of the
intratumoral vessels. The neoplastic cells possess an elongated tapered or cigar-shaped
nucleus, abundant pale eosinophilic cytoplasm, and distinct borders. In some lesions of
the nodular type of cutaneous adult myofibroma, there is a central sclerotic acellular area
surrounded by a more highly cellular area richly endowed with a slit-like vascular space.
The multinodular or biphasic type of adult cutaneous myofibroma displays multiple,

well-circumscribed nodules wherein spindle and plump cells are featured in whorls
(Fig. 53). Endothelium-lined vascular slits may be present at the periphery of some of the
nodules, or, alternately, areas of irregularly branching vascular channels may create the
appearance of a hemangiopericytoma. In contrast to infantile myofibromatosis, which
generally exhibits a characteristic zonation (the peripheral areas are composed of plump
spindle-shaped cells arranged in whorls, and the central areas show prominent vascular
hemangiopericytoma-like components and more primitive cells with vesicular nuclei,
eosinophilic cytoplasm, and indistinct cellular margins), the multinodular or biphasic
variant of cutaneous adult myofibroma shows a more haphazard arrangement or even
reversed zonation pattern. Neoplastic cells within the nodules are plump and elongated,
with a myofibroblastic appearance. They exhibit morphologic features of fibroblasts and
smooth muscle cells. In some nodules, the neoplastic cells blend with the smooth muscle
cells of the vessel walls, reminiscent of a vascular origin. A second population of more
immature mesenchymal cells impart, a pericytic appearance, as they surround the nod-
ules. Hyalinization of the stroma is more prominent in the center of the nodules and is a
characteristic feature of this multinodular variant of adult cutaneous myofibroma.
Aged lesions of cutaneous adult myofibroma have a leiomyomatous or fascicular
appearance. This leiomyoma-like or fascicular type of cutaneous adult myofibroma cre-
ates poorly circumscribed fascicles of spindle cells, with large pale eosinophilic cyto-
plasm and elongated tapering nucleus. The arrangement is haphazard, and it may
intermingle with thick collagen bundles and mucin. Vascularity is not prominent. Preex-
isting smooth muscle fascicles may appear entrapped within the lesion.
Immunohistochemically, the neoplastic cells of the cutaneous adult myofibroma show
strong expression of vimentin and both muscle-specific actin and α-smooth muscle actin,
whereas desmin is negative. The vascular markers CD31, CD34, and factor VIII-related
antigen stain the endothelium-lined vascular spaces but are not expressed by the neoplas-
tic cells (12).
Ultrastructurally, neoplastic cells of cutaneous adult myofibroma appear as
undifferentiated mesenchymal forms with features of fibroblasts, myofibroblasts, and
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