PATHOLOGY OF VASCULAR SKIN LESIONS - PART 10 doc

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References
1. Argenyi ZB, Piette WW, Goeken J. Cutaneous angiomyolipoma: a light microscopic, immunohis-
tochemical, and electron microscopic study [Abstract]. J Cutan Pathol 1986;13:434.
2. Argenyi ZB, Piette WW, Goeken JA. Cutaneous angiomyolipoma: a light microscopic, immunohis-
tochemical, and electron-microscopic study. Am J Dermatopathol 1991;13:497–502.
3. Mehregan DA, Mehregan DR, Mehregan AH. Angiomyolipoma. J Am Acad Dermatol 1992;27:331–3.
4. Rodriguez Fernandez A, Caro Mancilla A. Cutaneous angiomyolipoma with pleomorphic changes.
J Am Acad Dermatol 1993;29:115–6.
5. Val-Bernal FJ, Mira C. Cutaneous angiomyolipoma. J Cutan Pathol 1996;23:364–8.
6. Ortiz Rey JA, Valbuena Ruvira L, Bouso Montero M, Sacristan Lista F. Angiomiolipoma cutáneo.
Patología 1996;29:115–8.
7. Fitzpatrick JE, Mellette JR, Hwang RJ, Golitz LE, Zaim T, Clemous D. Cutaneous angiolipoleiomyoma.
J Am Acad Dermatol 1990;23:1093–8.
8. Buyukbabani N, Tetikkurt S, Ozturk AS. Cutaneous angiomyolipoma: report of two cases with emphasis
on HMB-45 utility. J Eur Acad Dermatol Venereol 1998;11:151–4.
9. Watanabe K, Suzuki T. Mucocutaneous angiomyolipoma. A report of 2 cases arising in the nasal cavity.
Arch Pathol Lab Med 1999;123:789–92.
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Chapter 10 / Other Neoplasms 293
Fig. 12. Clinical features of cutaneous angiomyxoma. A subcutaneous nodule on the dorsum
of the toe.
6. CUTANEOUS ANGIOMYXOMA
CLINICAL FEATURES
Cutaneous myxomas have been firmly established in recent years, especially when
they are present as part of Carney’s complex. This is an autosomal dominant complex
consisting of endocrine hyperactivity (Cushing’s syndrome, testicular tumors, and
acromegaly), spotty pigmentation, psammomatous melanotic schwannoma, and multiple
myxomas (cutaneous, cardiac, and mammary) (1–5). A patient with multiple cutaneous
myxomas and other anomalies of Carney’s complex progressed to scleromyxedema (6).
Multiple cutaneous myxomas, however, have also been described without other elements

of Carney’s complex (7,8). Solitary myxomas are not related to Carney’s complex and
may appear as cutaneous or subcutaneous nodules, especially in acral sites (9–11). When
there is a prominent vascular component, the lesion is designated angiomyxoma (9–11).
Clinically, cutaneous angiomyxomas appear as slow-growing nodules that have been
present for several years before excision (Fig. 12). Some solitary angiomyxomas appear
as congenital lesions (12), and, in rare instances, solitary cutaneous angiomyxoma may
be large (13).
H
ISTOPATHOLOGIC FEATURES
Histopathologically, the lesions are fairly well-circumscribed, multilobulated nod-
ules, with abundant blood vessels, especially at the periphery and delicate septa of col-
lagen bundles extending into the lesion (14). Individual nodules appear as sparsely cellular
with abundant mucinous material (Fig. 13). Stellate and spindle-shaped stromal cells are
scattered throughout the myxoid material. Cytologic atypia is mild at most, and mitotic
figures are rare. Sometimes dilated thin-walled blood vessels filled by erythrocytes are
scattered within the mucoid material, imparting an angiomatous appearance to the lesion.
Often, hyperplastic epithelia from entrapped adnexa, in the form of small epidermoid
cysts, thin strands of squamous epithelium, and small buds of basaloid cells, are seen
embedded in the lesion (14). A mixed inflammatory infiltrate is common, particularly
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Fig. 13. Histopathologic features of cutaneous angiomyxoma. (A) Low power shows an exophytic
lesion. The dermis exhibits a myxoid appearance. (B) Thin, spindle-shaped cells and capillaries
embedded in a myxoid stroma. (C) These spindle-shaped cells show no nuclear atypia.
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Chapter 10 / Other Neoplasms 295
stromal neutrophils, a feature unique to this neoplasm compared with other cutaneous
myxoid lesions (14). Immunohistochemical studies have shown that the cellular compo-
nent of the lesion is positive with vimentin and α-smooth muscle actin but negative for
CD34, S-100 protein, factor XIIIa, Leu-7, Kp1, MAC387, and desmin (10,14), support-

ing a myofibroblastic differentiation. Electron microscopic examination of these cells
demonstrated ultrastructural characteristics of fibroblasts (9).
Some cutaneous myxomas arise in the genital region (15), and they should be differen-
tiated from aggressive angiomyxoma. The latter lesion tends to be larger, extends to
deeper structures, and has a vascular component different from that of cutaneous
angiomyxoma, because the vascular component of aggressive angiomyxoma consists of
variable-sized vessels that range from small thin-walled capillaries to large vessels with
secondary changes including perivascular hyalinization and thick vessel walls.
T
REATMENT
Cutaneous angiomyxomas are benign neoplasms, but local recurrences have been
reported in 38% of cases (1,14), probably because they are subcutaneous and poorly
demarcated lesions.
References
1. Carney JA, Headington JT, Su WPD. Cutaneous myxomas: a major component of myxomas, spotty
pigmentation, and endocrine overactivity. Arch Dermatol 1986;122:790–8.
2. Carney JA. Psammomatous melanotic schwannoma: a distinctive heritable tumor with special associa-
tions, including cardiac myxoma and the Cushing syndrome. Am J Surg Pathol 1990;14:206–22.
3. Handley J, Carson D, Sloan J, et al. Multiple lentigines, myxoid tumour and endocrine overactivity; four
cases of Carney complex. Br J Dermatol 1992;126:367–71.
4. Carney JA. Carney complex: the complex of myxomas, spotty pigmentation, endocrine overactivity, and
schwannomas. Semin Dermatol 1995;14:90–8.
5. Egan CA, Stratakis CA, Turner ML. Multiple lentigines associated with cutaneous myxomas. J Am
Acad Dermatol 2001;44:282–4.
6. Craig NM, Putterman AM, Roenigk RK, Wang TD, Roenigk HH. Multiple periorbital cutaneous myxo-
mas progressing to scleromyxedema. J Am Acad Dermatol 1996;34:928–30.
7. Murphy CM, Grau-Massanes M, Sanchez RL. Multiple cutaneous myxomas. Report of a case without
other elements of Carney’s complex. J Cutan Pathol 1995;22:556–62.
8. Bernardeu K, Serpier H, Salmon Ehr V, Metz D, Pluot M, Kalis B. Myxomes cutanés multiples isolés.
Ann Dermatol Venereol 1998;125:30–3.

9. Allen PW, Dymock RB, MacCormac LB. Superficial angiomyxomas with and without epithelial com-
ponents. Am J Surg Pathol 1988;12:519–30.
10. Wilk M, Schmoeckel C, Kaiser HW, Hepple R, Kreysel HW. Cutaneous angiomyxoma: a benign
neoplasm distinct from cutaneous focal mucinosis. J Am Acad Dermatol 1995;33:352–5.
11. Alaiti S, Nelson FP, Ryoo JW. Solitary cutaneous myxoma. J Am Acad Dermatol 2000;43:377–9.
12. Bedlow AJ, Sampson SA, Holden CA. Congenital superficial angiomyxoma. Clin Exp Dermatol
1997;22:237–9.
13. Lockshin NA, Boswell JT. Giant cutaneous angiomyxoma. Cutis 1978;21:673–4.
14. Calonje E, Guerin D, McCormick D, Fletcher CD. Superficial angiomyxoma: clinicopathologic analysis
of a series of distinctive but poorly recognized cutaneous tumors with tendency for recurrence. Am J
Surg Pathol 1999;23:910–7.
15. Fetsch JF, Laskin WB, Tavassoli FA. Superficial angiomyxoma (cutanous myxoma): a clinicopatho-
logic study of 17 cases arising in the genital region. Int J Gynecol Pathol 1997;16:325–34.
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7. AGGRESSIVE ANGIOMYXOMA
CLINICAL FEATURES
An entirely different lesion from cutaneous angiomyxoma has been described by
Stepper and Rosai (1) under the term aggressive angiomyxoma. The lesion occurs in the
genital (Fig. 14), perineal, and pelvic regions, and women are chiefly affected (1–5), but
there have also been some reported examples in men involving the scrotum, perineal, and
perianal areas (6–8). Aggressive angiomyxomas are soft polypoid masses that show an
infiltrative growth but lack metastases.
H
ISTOPATHOLOGIC FEATURES
Histopathologically, the tumor is composed of stellate or spindle-shaped cells and
either thin or thick hyalinized vascular channels immersed within a myxoid matrix
that is rich in collagen bundles (Fig. 15). There is no cellular atypia or mitotic figures.
Immunohistochemically, the stromal cells of aggressive angiomyxoma express vimentin,
muscle specific actin, and α-smooth muscle actin (2,3,5–9). In addition, some studies

have demonstrated that the stromal cells were immunoreactive for desmin (3,5,7,9),
whereas myosin, CD34, factor VIII-related antigen, α1-antitrypsin, α1-antichymo-
trypsin, S-100 protein, neuron-specific enolase, estrogen and progesterone receptors, and
chromogranin were negative. Electron microscopic examination showed fibroblast-like
(2) or myofibroblast-like cells (1).
Recently, Fletcher et al. (10) have described angiomyofibroblastoma of the vulva, a
benign neoplasm distinct from aggressive angiomyxoma. According to these authors,
angiomyofibroblastoma is smaller, better circumscribed, more cellular, and has a more
abundant vascular component than aggressive angiomyxoma. Immunohistochemically,
the stromal cells of angiomyofibroblastoma are desmin-positive and actin-negative (10).
T
REATMENT
Wide local excision is recommended for aggressive angiomyxoma, but local recur-
rence is frequent because of the difficulty of excising of this poorly circumscribed neo-
plasm completely.
Fig. 14. Clinical features of aggressive angiomyxoma. A poorly circumscribed nodular lesion on
the pubis of an elderly woman.
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Chapter 10 / Other Neoplasms 297
Fig. 15. Histopathologic features of aggressive angiomyxoma. (A) Low power shows a poorly
circumscribed nodular lesion with a myxoid appearance involving the entire thickness of the
dermis. (B) Spindle cells embedded in a myxoid stroma. (C) Abundant dilated blood vessels are
another component of the lesion.
References
1. Steeper TA, Rosai J. Aggressive angiomyxoma of the female pelvis and perineum: report of nine cases
of a distinctive type of gynecologic soft-tissue neoplasm. Am J Surg Pathol 1983;7:463–75.
2. Begin LR, Clement PB, Kirk ME, et al. Aggressive angiomyxoma of pelvic soft part: a clinicopathologic
study of nine cases. Hum Pathol 1985;16:621–8.
3. Manivel C, Steeper T, Swanson P, Wick M. Aggressive angiomyxoma of the pelvis: an immuno-
peroxidase study [Abstract]. Lab Invest 1987;56:46A.

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4. Skalova A, Michal M, Husek K, Zamecnik M, Leivo I. Aggressive angiomyxoma of the pelvioperineal
region. Immunohistochemical and ultrastructural study of seven cases. Am J Dermatopathol
1993;15:446–51.
5. Fetsch JF, Laskin WB, Lefkowitz M, Kindblom LG, Meis-Kindblom JM. Aggressive angiomyxoma. A
clinicopathologic study of 29 female patients. Cancer 1996;78:79–90.
6. Tsang WYW, Chan JKC, Lee KC, et al. Aggressive angiomyxoma: a report of four cases occurring in
men. Am J Surg Pathol 1992;16:1059–65.
7. Clatch RJ, Drake WK, Gonzalez JG. Aggressive angiomyxoma in men: a report of two cases associated
with inguinal hernias. Arch Pathol Lab Med 1993;117:911–3.
8. Iezzoni JL, Fechner RE, Wong LS, Rosai J. Aggressive angiomyxoma in males. A report of four cases.
Am J Clin Pathol 1995;104:391–6.
9. Fetsch JF, Laskin WB, Lefkowitz M, et al. Aggressive angiomyxoma: a clinicopathologic study of 26
cases [Abstract]. Mod Pathol 1995;8:89A.
10 Fletcher CDM, Tsang WYW, Fisher C, Lee KC, Chan JKC. Angiomyofibroblastoma of the vulva. A
benign neoplasm distinct from aggressive angiomyxoma. Am J Surg Pathol 1992;16:373–82.
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Chapter 11 / Mistaken Vascular Neoplasms 299
299
11
Disorders Erroneously Considered
as Vascular Neoplasms
CONTENTS
KIMURA’S DISEASE
“MALIGNANT” ANGIOENDOTHELIOMATOSIS
(INTRAVASCULAR LYMPHOMATOSIS)
A
CRAL PSEUDOLYMPHOMATOUS ANGIOKERATOMA
IN CHILDREN (APACHE)

Table 1 summarizes a series of disparate disorders that have been erroneously consid-
ered as vascular neoplasms and are described in this chapter.
1. KIMURA’S DISEASE
CLINICAL FEATURES
Kimura’s disease is an inflammatory disorder of the soft tissue that consists of prolif-
erations of lymphoid and angiomatous tissues accompanied by lymphadenopathy,
peripheral blood eosinophilia, and elevated IgE levels. Kimura et al. (1) originally
described the disorder in 1948 as “an unusual granulation combined with hyperplastic
changes of lymphatic tissue.” Subsequently, several reports of the disorder appeared in
the literature, mostly in Oriental patients (2–8). It usually presents as a massive subcu-
taneous swelling (Fig. 1) preferentially located in periauricular and submandibular
regions of young men. The rare occurrence of Kimura’s disease in Caucasians caused
confusion between Kimura’s disease and angiolymphoid hyperplasia with eosinophilia.
In fact, Wells and Whimster (9), in their original description of angiolymphoid hyperpla-
sia with eosinophilia in 1969, linked this disorder to Kimura’s disease, considering
angiolymphoid hyperplasia to be late stage Kimura’s disease. After that, these terms were
used synonymously by several authors (10–15). Rosai et al. (16,17) were the first to note
that Kimura’s disease and angiolymphoid hyperplasia with eosinophilia are two differ-
Table 1
Disorders Erroneously Considered as Vascular Neoplasms
Kimura’s disease
“Malignant” angioendotheliomatosis (angiotropic or intravascular lymphoma)
APACHE (acral pseudolymphomatous angiokeratoma of children)
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Fig. 1. Clinical appearance of Kimura’s disease showing swelling of the left forehead of an adult man.
ent clinicopathologic entities. Recent reports have also supported this opinion (2–6,8,18).
According to these authors, the differential diagnosis between Kimura’s disease and
angiolymphoid hyperplasia with eosinophilia can be established on the basis of both
clinical and histopathologic features.

Clinically, Kimura’s disease occurs mainly in young men who present with large
swellings of the subcutaneous soft tissue. The disorder is frequently accompanied by
enlarged regional lymph nodes, nephrotic syndrome, peripheral blood eosinophilia, and
elevated serum IgE. This disease has a striking predilection for males. Patients with
Kimura’s disease also have elevated levels of interleukin (IL)-4, IL-5, and IL-13 mRNA
in peripheral blood mononuclear cells (19,20), and the Th2 cytokines probably play a role
in the development of this process. In contrast, angiolymphoid hyperplasia with eosino-
philia consists of papules or nodules with an angiomatous appearance which are located
superficially and which bleed easily. It is not accompanied by either lymphadenopathy
or peripheral blood eosinophilia, and the serum level of IgE is normal. In the cases
reported, one patient had Kimura’s disease associated with ulcerative colitis (20), and
another patient presented with lymphadenopathy, cutaneous nodules, and oral ulcer-
ations (21).
H
ISTOPATHOLOGIC FEATURES
Histopathologically, there are also several differences between angiolymphoid hyper-
plasia and Kimura’s disease. Viewed at low power, angiolymphoid hyperplasia with
eosinophilia appears as an angiomatous lesion, with thin- or thick-walled blood vessels
lined by prominent endothelial cells with a “histiocytoid” (16) or “epithelioid” (22,23)
appearance that characteristically show vacuolated cytoplasm. In contrast, low-power
views of lesions of Kimura’s disease show as a subcutaneous inflammatory disorder, with
lymphoid aggregates with prominent germinal center formation and infiltration of count-
less numbers of eosinophils (Fig. 2). The blood vessels in lesions of Kimura’s disease are
Fig. 2. (Opposite page) Histopathologic features of Kimura’s disease. (A) Low power shows
prominent germinal center formation involving the entire thickness of the dermis. (B) Germinal
centers show a central pale area and a peripheral ring of mature lymphocytes. (C) Numerous
eosinophils are present in the infiltrate.
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Chapter 11 / Mistaken Vascular Neoplasms 301
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abundant but never reach the degree of proliferation seen in angiolymphoid hyperplasia
with eosinophilia. Endothelial cells in blood vessels of Kimura’s disease may appear to
be prominent, and epithelioid and even to have cytoplasmic vacuoles, but these are focal
findings compared to the more universal alteration of the blood vessels in lesions of
angiolymphoid hyperplasia with eosinophilia. In short, Kimura’s disease seems to be an
inflammatory systemic process of unknown etiology rather than a disorder of blood
vessels.
An increased number of mast cells have been described in lesions of Kimura’s disease,
and it seems that the number of mast cells and the vascularity of the lesion run parallel,
with sparse numbers of mast cells and blood vessels in early lesions and a gradual increase
in fully developed lesions (24). Late stage lesions of Kimura’s disease exhibit a dense
hyaline fibrosis. Some authors have postulated that the slow release of mediators of
cytokines from mast cells by piecemeal degranulation may contribute to the patho-
mechanism of Kimura’s disease (25). Polymerase chain reaction investigations for human
herpesvirus 8 (HHV-8) yielded negative results in lesions of Kimura’s disease (26), and
DNA of Epstein-Barr virus has been detected in a single case (27).
T
REATMENT
Patients with Kimura’s disease are in good general health and have no evidence of
systemic lymphoreticular proliferation. Surgical excision of the lesions is often followed
by recurrences. Some patients with Kimura’s disease have been successfully treated with
cyclosporine (19,28) or pentoxifylline (21).
References
1. Kimura T, Yoshimura S, Ishikama E. On the unusual granulation combined with hyperplastic changes
of lymphatic tissues. Trans Soc Pathol Jpn 1948;37:178–80.
2. Kung ITM, Gibson JB, Bannatyne PM. Kimura’s disease: a clinicopathological study of 21 cases and
its distinction from angiolymphoid hyperplasia with eosinophilia. Pathology 1984;16:39–44.
3. Googe PB, Harris NL, Mihn, MC Jr. Kimura’s disease and angiolymphoid hyperplasia with eosino-
philia: two distinct histopathological entities. J Cutan Pathol 1987;14:263–71.

4. Urabe A, Tsuneyoshi M, Enjoji M. Epithelioid hemangioma versus Kimura’s disease: a comparative
clinicopathologic study. Am J Surg Pathol 1987;11:758–66.
5. Kuo T-T, Shih L-Y, Chan H-L. Kimura’s disease. Involvement of regional lymph nodes and distinction
from angiolymphoid hyperplasia with eosinophilia. Am J Surg Pathol 1988;12:843–54.
6. Chan JKC, Ng CS, Yuen NWF, Kung ITM, Gwi G. Epithelioid hemangioma (angiolymphoid hyperpla-
sia with eosinophilia) and Kimura’s disease in Chinese. Histopathology 1989;15:557–74.
7. Hui PK, Chan JK, Ng CS, et al. Lymphadenopathy of Kimura’s disease. Am J Surg Pathol 1989;
13:177–86.
8. Chun SI, Ji HG. Kimura’s disease and angiolymphoid hyperplasia with eosinophilia: clinical and his-
topathologic differences. J Am Acad Dermatol 1992;27:954–8.
9. Wells GC, Whimster IW. Subcutaneous angiolymphoid hyperplasia with eosinophilia. Br J Dermatol
1969;81:1–15.
10. Reed RJ, Terazakis N. Subcutaneous angioblastic lymphoid hyperplasia with eosinophilia (Kimura’s
disease). Cancer 1972;29:489–97.
11. Kim BM, Sithian N, Cucolo GF. Subcutaneous angiolymphoid hyperplasia (Kimura’s disease). Report
of a case. Arch Surg 1975;110:1246–8.
12. Buchner A, Silverman Jr S, Wara WM, Hansnen LS. Angiolymphoid hyperplasia with eosinophilia
(Kimura’s disease). Oral Surg 1980;49:309–13.
13. Thompson JW, Colman M, Williamson C, Ward PH. Angiolymphoid hyperplasia with eosinophilia of
the external ear canal. Treatment with laser excision. Arch Otolaryngol 1981;107:316–9.
14. Olsen TG, Helwig EB. Angiolymphoid hyperplasia with eosinophilia: a clinicopathologic study of 116
patients. J Am Acad Dermatol 1985;12:781–96.
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Chapter 11 / Mistaken Vascular Neoplasms 303
15. Eisenberg, E, Lowlicht R. Angiolymphoid hyperplasia with eosinophils: a clinicopathologic confer-
ence. J Oral Pathol 1985;14:216–23.
16. Rosai J, Gold J, Landy R. The histiocytoid hemangiomas. A unifying entity embracing several pre-
viously described entities of the skin, soft tissue, large vessels, bone, and heart. Hum Pathol 1979;
10:707–30.
17. Rosai J. Angiolymphoid hyperplasia with eosinophilia of the skin. Its nosological position in the spec-

trum of the histiocytoid hemangioma. Am J Dermatopathol 1982;4:175–84.
18. Helander SD, Peters MS, Kuo T-T, Su WPD. Kimura’s disease and angiolymphoid hyperplasia with
eosinophilia: new observations from immunohistochemical studies of lymphocyte markers, endothelial
antigens, and granulocyte proteins. J Cutan Pathol 1995;22:319–26.
19. Katagiri K, Itami S, Hatano Y, Yamaguchi T, Takayasu S. In vivo expression of IL-4, IL-5, IL-13 and
IFN-gamma mRNAs in peripheral blood mononuclear cells and effect of cyclosporin A in a patient with
Kimura’s disease. Br J Dermatol 1997;137:972–7.
20. Sugaya M, Suzuki T, Asahina A, Nakamura K, Ohtsuki M, Tamaki K. Kimura’s disease associated with
ulcerative colitis: detection of IL-5 mRNA expression of peripheral blood mononuclear cells and colon
lesion. Acta Derm Venereol 1998;78:375–7.
21. Hongcharu W, Baldassano M, Taylor CR. Kimura’s disease with oral ulcers: response to pentoxifylline.
J Am Acad Dermatol 2000;43:905–7.
22. Weiss SW, Enzinger FM. Epithelioid hemangioendothelioma. A vascular tumor often mistaken for a
carcinoma. Cancer 1982;50:970–81.
23. Weiss SW, Ishak KG, Dial DH, Sweet DE, Enzinger FM. Epithelioid hemangioendothelioma and
related lesions. Semin Diagn Pathol 1986;3:259–87.
24. Wong KT, Shamsol S. Quantitative study of mast cells in Kimura’s disease. J Cutan Pathol 1999;26:13–6.
25. Aoki M, Kawana S. The ultrastructural patterns of mast cell degranulation in Kimura’s disease. Derma-
tology 1999;199:35–9.
26. Jang KA, Ahn SJ, Choi JH, et al. Polymerase chain reaction (PCR) for human herpesvirus 8 and
heteroduplex PCR for clonality assessment in angiolymphoid hyperplasia with eosinophilia and
Kimura’s disease. J Cutan Pathol 2001;28:363–7.
27. Nagore E, Llorca J, Sanchez-Motilla JM, Ledesma E, Fortea JM, Aliaga A. Detection of Epstein-Barr
virus DNA in a patient with Kimura’s disease. Int J Dermatol 2000;39:618–20.
28. Kaneko K, Aoki M, Hattori S, Sato M, Kawana S. Successful treatment of Kimura’s disease with
cyclosporine. J Am Acad Dermatol 1999;41:893–4.
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2. “MALIGNANT” ANGIOENDOTHELIOMATOSIS
(INTRAVASCULAR LYMPHOMATOSIS)

CLINICAL FEATURES
“Malignant” angioendotheliomatosis, in contrast to reactive angioendotheliomatosis,
is an aggressive disease generally associated with progressive clinical manifestations
leading to the demise of the patient, usually less than a year after presentation. Until
recently, it was assumed that the cells within the blood vessels of malignant angio-
endotheliomatosis represented a proliferation of endothelial cells. However, immunohis-
tochemical and ultrastructural studies have established that these cells are neoplastic
lymphocytes, and the disorder is now named intravascular lymphomatosis. Approxi-
mately 100 cases have been reported in the literature (1–29), and in the past, a dozen
synonyms have been used to name this disorder (18).
Cutaneous lesions of intravascular lymphomatosis consist of tender erythematous or
purple nodules and plaques on the trunk and extremities (Fig. 3). In a patient with cuta-
neous hemangiomas and intravascular lymphoma, the lymphoma initially was clinically
confined to the hemangiomas of the skin; despite chemotherapy, the disease progressed,
and was fatal 23 months after initial diagnosis (29). Telangiectasia may be prominent
over the lesions. The disease most commonly affects older adults. More often, initial
signs of intravascular lymphomatosis are central nervous system disturbances, including
vision impairment, transient episodes of aphasia, weakness, hemiparesis, sensory loss,
seizures, and progressive dementia (3,6,24). Intravascular lymphomatosis is a rapidly
fatal disease with secondary involvement of the liver, lungs, spleen, adrenal, thyroid, and
kidneys (4,12).
H
ISTOPATHOLOGIC FEATURES
Histopathologically, cutaneous lesions of intravascular lymphomatosis consist of
dilated blood vessels in the dermis and subcutaneous fat that appear to be filled with
highly atypical cells, with hyperchromatic nuclei and numerous mitotic figures (Fig. 4).
These cells may be enmeshed in fibrin platelet thrombi. The lumen of the larger involved
vessels may be thrown into folds, resulting in a glomeruloid appearance. Extension of the
infiltrate into vessel walls or perivascular connective tissue is a frequent feature.
Originally, intravascular cells in malignant angioendotheliomatosis were considered

to be endothelial cells, and some initial immunohistochemical studies reported factor
VIII-related antigen positivity in intraluminal cells (13,23). Ultrastructural studies iden-
tified Weibel-Palade bodies (23,24), also supporting an endothelial nature for intravas-
cular neoplastic cells. However, most immunohistochemical studies failed to demonstrate
factor VIII related antigen reactivity in intravascular cells (1,5,7,11,12,18,20,21,26,27),
and Ulex europaeus I lectin has consistently failed to bind to either intravascular or
extravascular infiltrates (1,11,12,14,21,26,27). Previous studies describing factor VIII-
related antigen staining have been attributed to nonspecific staining, owing to adsorption
of platelet-derived factor VIII-related antigen by tumor cells embedded in fibrin platelet
thrombi (1,8,11,12,15), or staining of endothelial cells that appeared intraluminally
because of the complex intraluminal folding of the affected blood vessel (19). Further-
more, additional immunohistochemical studies have demonstrated beyond any doubt
that intraluminal neoplastic cells in malignant angioendotheliomatosis express immu-
noreactivity for leukocyte markers (1,2,7,9,12,14,22,26,27).
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Chapter 11 / Mistaken Vascular Neoplasms 305
Fig. 3. Clinical features of intravascular lymphomatosis. (A) Multiple nodules on the left flank of
a young man. (B) Subcutaneous nodules on the posterior left knee.
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Most of the cases of intravascular lymphomatosis subjected to immunophenotyping
studies showed a B-cell phenotype (1,7,9,10,16,17,19,22), but cases with a T-cell phe-
notype have also been described (9,21,22,26,27). In rare instances, neoplastic cells were
negative for all pertinent markers, and their nature remains uncertain (12). Genotypic
Fig. 4. Histopathologic features of intravascular lymphomatosis. (A) Low power shows cellular
aggregations at different levels of the dermis. (B) Higher magnification demonstrates that these
cellular aggregations are within vascular lumina. (C) Still higher magnification demonstrates that
many of the cells in the vascular lumina show pleomorphic and hyperchromatic nuclei and frequent
mitotic figures. (D) Immunohistochemical studies demonstrate that intraluminal cells express
immunoreactivity for the lymphocytic marker leukocyte commom antigen.

11/Sangüeza/299-310/F 01/14/2003, 4:28 PM306
Chapter 11 / Mistaken Vascular Neoplasms 307
analysis has been reported for four cases, three demonstrating clonal rearrangement of the
immunoglobulin gene (17,19,28), and the fourth clonal T-cell receptor rearrangement
(21). Similar conclusions have been reached from ultrastructural studies, and initial
reports supporting an endothelial nature for intravascular proliferating cells (3,6,23,24),
have been critically reviewed. It seems likely that these investigators mistook reactive
endothelial cells for the malignant cells in question (7,11,12).
T
REATMENT
Although isolated patients with intravascular lymphomatosis have responded to treat-
ment with chemotherapy (9,25), the prognosis of the disease is poor, and most patients
die within a year of presentation.
R
EFERENCES
1. Wick MR, Rocamora A. Reactive and malignant “angioendotheliomatosis”: a discriminant clinico-
pathologic study. J Cutan Pathol 1988;15:260–71.
2. Ansell J, Bhawan J, Cohen S, et al. Histiocytic lymphoma and malignant angioendotheliomatosis. One
disease or two? Cancer 1982;50:1506–12.
3. Scott PWB, Silvers DN, Helwig EB. Proliferating angioendotheliomatosis. Arch Pathol 1975;99:323–6.
4. Braverman I, Lerner AB. Diffuse malignant proliferation of vascular endothelium. A possible new
clinical and pathologic entity. Arch Dermatol 1961;84:72–80.
5. Yamamura Y, Akamizu H, Hirata T, Kito S, Hamada T. Malignant lymphoma presenting with neoplastic
angioendotheliosis of the central nervous system. Clin Neuropathol 1983;2:62–8.
6. Wick MR, Scheithaver BW, Okazaki H, et al. Cerebral angioendotheliomatosis. Arch Pathol Lab Med
1982;106:342–6.
7. Bhawan J, Wolff SM, Ucci AA, et al. Malignant lymphoma and malignant angioendotheliomatosis: one
disease. Cancer 1985;55:570–6.
8. Dominguez FE, Rosen LB, Kramer HC. Malignant angioendotheliomatosis proliferans. Am J
Dermatopathol 1986;8:419–25.

9. Sheibani K, Battifora H, Winberg CD, et al. Further evidence that “malignant angioendotheliomatosis”
is an angiotropic large-call lymphoma. N Engl J Med 1986;314:943–8.
10. Willemze R, Kroyswijk MRJ, Debruin CD, et al. Angiotropic (intravascular) large cell lymphoma of the
skin previously classified as malignant angioendotheliomatosis. Br J Dermatol 1987;116:393–9.
11. Wrotnowski U, Mills SE, Cooper PH. Malignant angioendotheliomatosis. An angiotropic lymphoma.
Am J Clin Pathol 1985;83:244–8.
12. Wick MR, Mills SE, Scheithauer BW, et al. Reassessment of malignant “angioendotheliomatosis:”
evidence in favor of its reclassification as “intravascular lymphomatosis.” Am J Surg Pathol
1986;10:112–3.
13. Fulling KH, Gersell DJ. Neoplastic angioendotheliomatosis: histologic, immunohistochemical, and
ultrastructural findings in two cases. Cancer 1982;51:1107–18.
14. Carroll TJ, Schelper RL, Goeken JA, et al. Neoplastic angioendotheliomatosis: immunopathologic and
morphologic evidence for intravascular malignant lymphomatosis. Am J Clin Pathol 1986;85:169–75.
15. Mori S, Itoyama S, Mohri N, et al. Cellular characteristics of neoplastic angioendotheliomatosis. An
immunohistochemical marker study of 6 cases. Virchows Arch Pathol Anat 1985;407:167–75.
16. Ferry JA, Harris NL, Picker LJ, et al. Intravascular lymphomatosis (malignant angioendotheliomatosis).
A B-cell neoplasm expressing surface homing receptor. Mod Pathol 1988;1:444–52.
17. Otrakji CL, Voight W, Amador A, et al. Malignant angioendotheliomatosis: a true lymphoma. A case
of intravascular malignant lymphomatosis studied by Southern blot hybridization analysis. Hum Pathol
1988;19:475–8.
18. Bhawan J. Angioendotheliomatosis proliferans systemisata: an angiotropic neoplasm of lymphoid ori-
gin. Semin Diagn Pathol 1987;4:18–27.
19. Petroff N, Koger OW, Fleming MG, et al. Malignant angioendotheliomatosis: an angiotropic lym-
phoma. J Am Acad Dermatol 1989;21:727–33.
20. Molina A, Lombard C, Donlon T, Bangs CD, Dorfman RF. Immunohistochemical and cytogenetic
studies indicate that malignant angioendotheliomatosis is a primary intravascular (angiotropic) lym-
phoma. Cancer 1990;66:474–9.
11/Sangüeza/299-310/F 01/14/2003, 4:28 PM307
308 Sangüeza and Requena / Pathology of Vascular Skin Lesions
21. Sepp N, Schuler G, Romani N, et al. “Intravascular lymphomatosis” (angioendotheliomatosis): evi-

dence for a T-cell origin in two cases. Hum Pathol 1990;21:1051–8.
22. Hisashi T, Tadaaki E, Toyohiro T, Masuzou K, Yokio F, Syouji K. Congenital angiotropic lymphoma
(intravascular lymphomatosis) of the T-cell type. Cancer 1991;67:2131–6.
23. Kitagawa M, Matsubara O, Song SY, et al. Neoplastic angioendotheliomatosis. Immunohistochemical
and electron microscopic findings in three cases. Cancer 1985;56:1134–43.
24. Petito CK, Gottlieb GJ, Dougherty JH, et al. Neoplastic angioendotheliomatosis: Ultrastructural study
and review of the literature. Ann Neurol 1978;3:393–9.
25. Keahey TM, Guerry D IV, Tuthill RJ, Bondi EE. Malignant angioendotheliomatosis proliferans treated
with doxorubicin. Arch Dermatol 1982;118:512–4.
26. Setoyama M, Mizoguchi S, Orikawa T, Tashiro M. A case of intravascular malignant lymphomatosis
(angiotropic large-cell lymphoma) presenting memory T-cell phenotype and its expression of adhesion
molecules. J Dermatol 1992;19:263–9.
27. Sangueza O, Hyder DM, Sangueza P. Intravascular lymphomatosis: report of an unusual case with
T-cell phenotype occurring in an adolescent male. J Cutan Pathol 1992;19:226–31.
28. Kamesaki H, Matsui Y, Ohno Y, et al. Single case report: angiocentric lymphoma with histologic
features of neoplastic angioendotheliomatosis presenting with predominant respiratory and hematologic
manifestations. Am J Clin Pathol 1990;94:768–72.
29. Rubin MA, Cossman J, Freter CE, Azumi N. Intravascular large cell lymphoma coexisting within
hemangiomas of the skin. Am J Surg Pathol 1997;21:860–4.
11/Sangüeza/299-310/F 01/14/2003, 4:28 PM308
Chapter 11 / Mistaken Vascular Neoplasms 309
3. ACRAL PSEUDOLYMPHOMATOUS ANGIOKERATOMA
IN CHILDREN (APACHE)
CLINICAL FEATURES
Ramsay et al. (1,2) have described a group of children presenting with unilateral,
multiple, persistent angiomatous papules on acral regions of the hands and feet, termed
acral pseudolymphomatous angiokeratoma in children (APACHE). The histopathology
of the lesions revealed a well-circumscribed, dermal lymphohistiocytic infiltrate with
prominent thickened capillaries. An additional case has been reported by Hara et al. (3).
H

ISTOPATHOLOGIC FEATURES
Histopathologically, lesions consisted of the presence of a subepidermal, well-circum-
scribed, dense, nodular lymphohistiocytic infiltrate with occasional plasma cells, eosi-
nophils, and a few multinucleated giant cells. Prominent capillaries are noted within and
around the infiltrate (Fig. 5) Immunohistochemistry revealed the main cellular compo-
nents to be an admixture of B- and T-lymphocytes (2,4), and, according to Kaddu et al.
(4), lesions of APACHE are better interpreted as a variant of cutaneous pseudolymphoma
rather than an angiokeratoma.
T
REATMENT
Simple excision of the lesions is curative.
References
1. Ramsay B, Dahl MGC, Malcolm AJ, Soyer HP, Wilson Jones E. Acral pseudolymphomatous
angiokeratoma of children (APACHE). Br J Dermatol 1988;119(suppl 33):13.
2. Ramsay B, Dahl MGC, Malcolm AJ, Wilson Jones E. Acral pseudolymphomatous angiokeratoma of
children. Arch Dermatol 1990;126:1524–5.
3. Hara M, Matsunaga J, Tagami H. Acral pseudolymphomatous angiokeratoma of children (APACHE):
a case report and immunohistologic study. Br J Dermatol 1991;124:387–8.
4. Kaddu S, Cerroni L, Pilatti A, Soyer HP, Kerl H. Acral pseudolymphomatous angiokeratoma. A variant
of cutaneous pseudolymphomas. Am J Dermatopathol 1994;16:130–3.
Fig. 5. Histopathologic features of APACHE. (A) Low power magnification showing dense
infiltrates within the dermis admixed with vessels. (Continued)
11/Sangüeza/299-310/F 01/14/2003, 4:28 PM309
310 Sangüeza and Requena / Pathology of Vascular Skin Lesions
Fig. 5. Histopathologic features of APACHE. (B) The infiltrates are composed of uniform lym-
phocytes, whereas the vessels show thick walls and prominent endothelial cells. (C) Other areas
show a predominant vascular component.
11/Sangüeza/299-310/F 01/14/2003, 4:28 PM310
Index 311
311

INDEX
Acquired acral fibrokeratoma, 279
Acquired elastotic hemangioma, 174
clinical features, 174
histopathologic features, 174–175
immunohistochemistry, 174
treatment, 175
Acral pseudolymphomatous angiokeratoma in
children (APACHE)
histopathologic features, 309, 310
treatment, 309
Acroangiodermatitis of Mali, 123–124,
125–126
Acrosyringium, 2
Aggressive angiomyxoma
cutaneous angiomyxoma and, 295, 296
histopathologic features, 296, 297, 298
immunohistochemistry, 296
Alopecia areata, 37
Amniotic fluid, 1
Angioblastoma, 164
Angioendothelioma
endovascular papillary, see Dabska’s tumor
papillary intralymphatic, see Dabska’s tumor
Angioendotheliomatosis, 128
malignant, 128, see also Intravascular lym-
phomatosis
reactive, see Reactive angioendotheliomatosis
Angiofibroblastoma of the vulva, 296
Angiofibroma

clinical features, 279–280
histopathologic features, 280–282
immunohistochemistry, 282
treatment, 282
Angiokeratoma, 47, 64, 86
acral pseudolymphomatous in children
(APACHE), 309, 310
circumscriptum, 86
clinical features, 86–89
corporis diffusum, 87–88, 89, 90, 91, see also
Fabry’s disease
Fordyce’s, 86, 90
histopathologic features, 89–91, 92
Mibelli’s, 87
treatment, 91
Angioleiomyoma
clinical features, 284
epithelioid, 286
histopathologic features, 284–286
immunohistochemistry, 284, 286
intravascular, 286
palisaded, 286
treatment, 286
Angiolipoma
cellular, 288
clinical features, 287
histopathologic features, 287–289
infiltrating, 288
lipoma vs., 287
multiple, 287

subcutaneous, 288
treatment, 289
Angiolymphoid hyperplasia with eosinophilia
(AHE)
clinical features, 99–100
differential diagnosis, 102
HHV8 and, 99
histopathologic features, 100–102
immunohistochemistry, 102
Kimura’s disease and, 99, 102, 299–300
nevus flammeus and, 43
treatment, 102
Angioma
cherry, see Cherry angioma
choroidal, 39
spider, see Spider angioma
sudoriparous, 23
tufted, see Tufted angioma
Angioma serpiginosum, 133
atypical, 134
clinical features, 133–134
histopathologic features, 134
treatment, 134
Angiomatosis
bacillary, see Bacillary angiomatosis
bilateral retinal, 42
epithelioid, 112
homolateral leptomeningeal, 39–40
ipsilateral leptomeningeal, 39
Sangueza_Index_Final 01/14/2003, 5:44 PM311

312 Index
Angiomyxoma, 293, see also Aggressive
angiomyxoma; Cutaneous
angiomyxoma
Angiosarcoma
CD31 and, 8
CD34 and, 8
cutaneous, associated with lymphedema, see
Cutaneous angiosarcoma associated with
lymphedema
cutaneous, of the face and scalp, see Cutaneous
angiosarcoma of the face and scalp
cutaneous, radiation-induced, see Radiation-
induced cutaneous angiosarcoma
epithelioid, see Epithelioid angiosarcoma
VEGFR-3 and, 8
vWF and, 7
Wilson Jones’, see Cutaneous angiosarcoma of
the face and scalp
Antigens
CD1, 2
factor VIII-related, 7
human leukocyte,-DR, 2
Apocrine glands, 2
Arteries
adventitia, 5
intima, 4–5
media, 5
Arteriovenous hemangioma, 154
clinical features, 154, 155

histopathologic features, 154, 155
inflammatory, 99
treatment, 154
Ataxia-telangiectasia, 82, 84
Atypical pyogenic granuloma, 99
Atypical vascular lesions, 195
radiation-induced cutaneous angiosarcoma and,
262
Bacillary angiomatosis, 112
clinical features, 112
histopathologic features, 113, 114
Kaposi’s sarcoma and, 112
treatment, 113
verruga peruana and, 116
Bannayan-Riley-Ruvalcaba syndrome, 57, 59
Bannayan-Zonana syndrome, 56
Bartonella
bacilliformis, 116
henselae, 112
quintana, 112
Bartonellosis, 116
Beckwith-Wiedemann syndrome, 42
Benign atypical vascular lesions of the lip, 120
Benign lymphangioendothelioma, 191, 195
clinical features, 191–192
differential diagnosis, 192
histopathologic features, 192, 193
hobnail hemangioma and, 157
immunohistochemistry, 192
Kaposi’s sarcoma and, 192, 196, 229

radiation-induced cutaneous angiosarcoma and,
262
treatment, 192
Benign lymphangiomatous papules, 195
radiation-induced cutaneous angiosarcoma and,
262
Benign neonatal hemangiomatosis, 141
Benign vascular proliferations
radiation-induced cutaneous angiosarcoma and,
262
Benign vascular proliferations, in irradiated skin,
195
clinical features, 195
histopathologic features, 195–197
treatment, 197
Birbeck granules, 2
Birt-Hogg-Dube syndrome, 287
Blue capillary sponge blebs, 51
Blue rubber bleb nevus syndrome, 52–53, 57, 59,
198
Bockenheimer’s syndrome, 34
Café-au-lait macules, 54
Campbell de Morgan spots, 151
Capillary aneurysm, 76
clinical features, 76
histopathologic features, 76–78
treatment, 78
Carcinoembryonic antigen (CEA), 8
Carcinomas, 7
Carney’s complex, 293

Carrion’s disease, 116
Castleman’s disease, 169, 219
Cat scratch disease, 112
CD1, 2
CD31, 7, 8
CD34, 7, 8
Cherry angioma
clinical features, 151
histopathologic features, 151–152
immunohistochemistry, 151
treatment, 152
Chondrosarcoma, 54–55
Choroidal angioma, 39
Cirsoid aneurysm, 154
Coats’ disease, 42
Cobb’s syndrome, 41
Sangueza_Index_Final 01/14/2003, 5:44 PM312
Index 313
Collagen, embryological, 2
Composite hemangioendothelioma
clinical features, 250
histopathologic features, 250
immunohistochemistry, 250
treatment, 250
Cornification, 1–2
Cowden disease, 57
Crow-Fukase syndrome, 169
Cutaneous angiolipoleiomyoma
clinical features, 290
histopathologic features, 290–291

immunohistochemistry, 290
treatment, 292
Cutaneous angiomyxoma
aggressive angiomyxoma and, 295, 296
Carney’s complex and, 293
clinical features, 293
immunohistochemistry, 295
treatment, 295
Cutaneous angiosarcoma, radiation-induced, see
Radiation-induced cutaneous angiosarcoma
Cutaneous angiosarcoma associated with lymphe-
dema, 258
clinical features, 258
differential diagnosis, 259–60
histopathologic features, 258–260
immunohistochemistry, 259–60
treatment, 260
Cutaneous angiosarcoma of the face and scalp, 251
clinical features, 251–252, 253 fig
immunohistochemistry, 253, 255
Kaposi’s sarcoma and, 251–252
treatment, 255
Cutaneous collagenous vasculopathy, 82, 83, 84
Cutaneous histiocytoid hemangioma, 99
Cutaneous myofibroma, 212
clinical features, 212
histopathologic features, 212–215
immunohistochemistry, 213
pericytes and, 215
treatment, 215

Cutaneous pseudolymphoma, 309
Cutis marmorata telangiectatica congenita
(CMTC), 32
anomalies associated with, 33
clinical features, 32–33
differential diagnosis, 34
histopathologic features, 33–34
treatment, 34
Cystic hygromas, see Cystic lymphatic malforma-
tions
Cystic lymphatic malformations, 54, 67
clinical features, 67
histopathologic features, 67, 68 fig.
superficial lymphatic malformations vs., 67
treatment, 68
Cytogenetic studies, 12
Cytokeratin, 7
Cytomegalovirus (CMV), 218
Dabska’s tumor
angiosarcoma and, 243
clinical features, 241
glomeruloid hemangioma and, 172, 243
histopathologic features, 241–243
hobnail hemangioendothelioma and, 241, 243
hobnail hemangioma and, 157
immunohistochemistry, 243
retiform hemangioendothelioma and, 243
treatment, 243–244
VEGFR-3 and, 8, 243
Dermatofibroma

epithelioid, 236
multinucleate cell angiohistiocytoma and, 276–
277
Dermatofibrosarcoma protuberans, 8
Dermis
blood supply, 2–3
composition, 2
embryological development of, 1, 2
Digital verrucous fibroangioma, 47
Disseminated eruptive hemangiomas, 139
Disseminated hemangiomatosis, 139
Eccrine angiomatous hamartoma (EAH), 19, 23
clinical features, 23–24
histopathologic features, 24
immunohistochemistry, 24
treatment, 24
Eccrine glands, 2
Ectoderm, 1
Embryo, skin of, 1–2
Endothelial cells, 5
Endovascular papillary angioendothelioma, see
Dabska’s tumor
Epidermis, 1, 2
Epithelioid angioleiomyoma, 286
Epithelioid angiomatosis, 112
Epithelioid angiosarcoma, 7
clinical features, 268
histopathologic features, 268–269
immunohistochemistry, 268
treatment, 270

Epithelioid dermatofibroma, 236
Epithelioid hemangioendothelioma, 236
carcinoma and, 7
clinical features, 236–237
Sangueza_Index_Final 01/14/2003, 5:44 PM313
314 Index
differential diagnosis, 237, 239
eccrine syringofibroadenoma and, 237
GLUT-1 and, 10
histopathologic features, 237–239
immunohistochemistry, 237, 239
kaposiform hemangioendothelioma and, 236
retiform hemangioendothelioma and, 236
spindle-cell hemangioma and, 186, 236
treatment, 239
vWF and, 7
Epithelioid hemangioma, 99
Epithelium, embryologic, 1
Epulis gravidarum, 106
Fabry’s disease, 56, 88–89, 90, 91, 92, see also
Angiokeratoma: corporis diffusum
Factor VIII-related antigen, 7
Fibroangioma
digital verrucous, 47
Fibrokeratoma
acquired acral, 279
Fibrous papule of the nose, 279, 280
Fordyce’s angiokeratoma, 86, 90
Generalized essential telangiectasia, 80, 83
histopathologic features, 82–83

Giant-cell angioblastoma
clinical features, 184
hemangiopericytoma and, 184
histopathologic features, 184, 185
treatment, 184
Glaucoma, 38–39
Glomangiomas, 57, 198, 201
Glomangiomyoma, 201
Glomangiosarcoma, 271–273
clinical features, 271
differential diagnosis, 273
hemangiopericytoma and, 273
histopathologic features, 271–273
immunohistochemistry, 271, 273
leiomyosarcoma and, 273
nodular hidradenoma and, 273
treatment, 273
Glomeruloid hemangioma, 169
clinical features, 169
differential diagnosis, 171–172
endovascular papillary angioendothelioma and,
172, 243
histogenesis, 169–170
histopathologic features, 169–172
immunochemistry, 169
intravascular papillary endothelial hyperplasia
and, 171–172
intravascular pyogenic granuloma and, 171
treatment, 172
Glomus bodies, 5

Glomus cells, 5
Glomus tumors, 198
apocrine hidradenomas and, 202
blue rubber bleb nevus syndrome and, 198
clinical features, 198–199, 201 fig.
glomangiomas and, 198, 201
glomangiomyomas and, 201
histopathologic features, 199–202, 203–205
immunohistochemistry, 201–202
Kasabach-Merritt syndrome and, 198
malignant, see Glomangiosarcoma
as pericytes, 201
treatment, 202
GLUT-1, 7, 8, 10
Gorham’s syndrome, 56, 59
Graves’ disease, 80
Hair follicles, 2
Hamartoma
defined, 19
eccrine angiomatous, see Eccrine angiomatous
hamartoma (EAH)
Hemangioendothelioma, 18
CD31 and, 8
composite, see Composite hemangioendothe-
lioma
epithelioid, see Epithelioid hemangioendothe-
lioma
hobnail, see Hobnail hemangioendothelioma
kaposiform, see Kaposiform hemangioendothe-
lioma

polymorphous, 250
retiform, see Retiform hemangioendothelioma
spindle cell, see Spindle cell hemangioma
Hemangioma, 15
acquired elastotic, see Acquired elastotic
hemangioma
arteriovenous, see Arteriovenous heman-
gioma
cavernous, 51
CD31 and, 8
congenital, 142
congenital nonprogressive, 142–143
cutaneous histiocytoid, 99
disseminated eruptive, 139
epithelioid, 99
glomeruloid, see Glomeruloid hemangioma
histiocytoid, 99
hobnail, see Hobnail hemangioma
infantile, see Infantile hemangioma
Sangueza_Index_Final 01/14/2003, 5:44 PM314
Index 315
intramuscular, 288
lobular capillary, 105
microvenular, see Microvenular hemangioma
miliary, 139
multiple cutaneous, 140–141
noninvoluting congenital, 142
progressive capillary, 164
sinusoidal, see Sinusoidal hemangioma
spindle cell, see Spindle cell hemangioma

targetoid hemosiderotic, see Hobnail heman-
gioma
verrucous, 47
visceral, 139–141
Hemangiomatosis
benign neonatal, 141
disseminated, 139
neonatal, 139
Hemangiopericytoma, 208
clinical features, 208
giant-cell angioblastoma and, 184
glomangiosarcoma and, 273
histopathologic features, 208–210
immunohistochemistry, 209–210
infantile myofibromatosis and, 209
treatment, 210
Hereditary benign telangiectasia, 82, 83
Hereditary hemorrhagic telangiectasia, 81–82
histopathologic features, 82–83
treatment, 83–84
Hibernoma, 289
Hidradenoma
apocrine, 202
nodular, 273
Histiocytoid hemangioma, 99
Histochemical stains, 7
Hobnail hemangioendothelioma, 241, 243
Hobnail hemangioma, 157
benign lymphangioendothelioma and, 157
clinical features, 157

Dabska’s tumor and, 157
differential diagnosis, 159
histopathologic features, 157–159
immunohistochemistry, 159
Kaposi’s sarcoma and, 157, 159, 229
retiform hemangioendothelioma and, 157
treatment, 159
VEGFR-3 and, 8, 159
Hodgkin’s disease, 106
Human hematopoietic progenitor cell antigen, see
CD34
Human herpesvirus-8 (HHV-8), 219
AHE and, 99
Kaposi’s sarcoma and, 11
Human leukocyte antigen-DR, 2
Human papillomavirus (HPV), 218
Hyperkeratotic capillary-lymphatic malformations,
86
Hyperkeratotic vascular malformations, 134
Hyperkeratotic vascular stains, 47
clinical features, 47, 48
histopathologic features, 47, 49
treatment, 47
Hyperplasia, 15
Hypochromic nevus, 29
Hypomelanosis, 29
Immunohistochemical stains, 7–10, see also
subheading immunohistochemistry under
names of lesions
Infantile hemangioma, 15, 136

capillary, 15, 18, 136
cavernous, 15, 18, 136
clinical features, 136–141
deep, 136
GLUT-1 and, 10, 145
histopathologic features, 141–145
immunohistochemistry, 143, 145
kaposiform hemangioendothelioma and, 177
Kasabach-Merritt syndrome and, 138–139,
145–46
mixed, 136
prevalence, 137
stages, 137–138
superficial, 136
treatment, 145–146
tufted angioma and, 166
VEGFR-3 and, 8, 143
Infantile myofibromatosis, 209, 212
Inflammatory angiomatous nodule, 99
Intramuscular hemangioma, 288
Intravascular angioleiomyoma, 286
Intravascular lymphomatosis
clinical features, 304, 305
histopathologic features, 304, 306–307
immunohistochemistry, 304
treatment, 307
Intravascular papillary endothelial hyperplasia
(IPEH), 119
clinical features, 119
glomeruloid hemangioma and, 171–172

histopathologic features, 119–120, 121
Kaposi’s sarcoma and, 119
Stewart-Treves syndrome and, 119
treatment, 120
Intravascular pyogenic granuloma
glomeruloid hemangioma and, 171
Intravenous atypical vascular proliferation, 99
Sangueza_Index_Final 01/14/2003, 5:44 PM315
316 Index
Kaposiform hemangioendothelioma
clinical features, 177
epithelioid hemangioendothelioma and, 236
GLUT-1 and, 10
histopathologic features, 177–180
immunohistochemistry, 178
infantile hemangioma and, 177
Kaposi’s sarcoma and, 177, 230
Kasabach-Merritt syndrome and, 177
treatment, 180
tufted angioma and, 166, 177
VEGFR-3 and, 8, 178
Kaposi’s sarcoma, 59, 217–219
African-endemic variant, 218, 219
AIDS-associated, 218, 220–222
bacillary angiomatosis and, 112
benign lymphangioendothelioma and, 192, 196,
229
CD31 and, 8
CD34 and, 8, 229
classic, 218, 219, 222

clinical features, 219–222, 223, 224
cutaneous angiosarcoma of the face and scalp
and, 251–252
cytomegalovirus (CMV) and, 218
differential diagnosis, 229–230
HHV-8 and, 11
histogenesis, 228
histopathologic features, 222–230
hobnail hemangioma and, 157, 159, 229
HPV antigens and, 218
hyaline globules in, 228
immunohistochemistry, 218, 228–229
immunosuppressive form of, 218, 219–220
IPEH and, 119
kaposiform hemangioendothelioma and, 177,
230
microvenular hemangioma and, 161–162
nodular, 225, 227–228
patch stage, 222–24, 228
pathogenesis, 219
spindle cell hemangioma and, 188, 230
spindle cells, 224–225, 229
treatment, 230
VEGFR-3 and, 8, 229
Kaposi’s sarcoma-associated herpes virus (KSHV),
11
Kasabach-Merritt syndrome, 47, 138–139, 145–146
glomus tumors and, 198
kaposiform hemangioendothelioma and, 177
tufted angioma and, 164, 166

Keratohyalin granules, 2
Kimura’s disease
AHE and, 99, 102, 299–300
clinical features, 299–300
histopathologic features, 300–302
treatment, 302
Klippel-Trenaunay syndrome, 19, 40, 55–56, 59,
89, 186
Langerhans cells, 2
Leiomyosarcoma
glomangiosarcoma and, 273
Linear telangiectasia, 79
Lipoblastoma, 289
Louis-Bar syndrome, 82
Lymphangiectases, 195
clinical features, 95
histopathologic features, 95–96
radiation-induced cutaneous angiosarcoma and,
262
treatment, 96
Lymphangioma, 63, 195
acquired progressive, 191
circumscriptum, 63, 195
radiation-induced cutaneous angiosarcoma and,
262
Lymphangiomatosis, 70
clinical features, 70
histopathologic features, 70–72
immunohistochemistry, 72
treatment, 72

Lymphangiosarcomas, 258
Lymphedema
angiosarcoma associated with, see Cutaneous
angiosarcoma associated with lymphedema
cutaneous angiosarcoma associated with, see
Cutaneous angiosarcoma associated with
lymphedema
Maffucci’s syndrome, 53–55, 58–59, 67, 186, 188
Malformation, defined, 27
Malignant angioendotheliomatosis, 128, see also
Intravascular lymphomatosis
Malignant glomus tumor (MGT), see
Glomangiosarcoma
Melanoblasts, 2
Melanocytes, 2, 20
Merkel cells, 2
Mesoderm, 1
Mibelli’s angiokeratoma, 87
Microvenular hemangioma, 161
clinical features, 161
differential diagnosis, 161–62
histopathologic features, 161–162
Kaposi’s sarcoma and, 161–162
Sangueza_Index_Final 01/14/2003, 5:44 PM316