In addition to lymphedema secondary to mastectomy, this type of angiosarcoma has also been described in areas of lymphedema secondary to a variety of other mechanisms, including axillary
Trang 17 CUTANEOUS ANGIOSARCOMA ASSOCIATED
WITH LYMPHEDEMA
Stewart and Treves (1) first described the development of cutaneous angiosarcoma in
lymphedematous areas in 1948 Since then, this disorder has been known as Treves syndrome In their original report, these authors reported six patients withpostmastectomy lymphedema on the ipsilateral arm in whom angiosarcomas developedseveral years after this procedure A large number of additional cases rapidly appeared
Stewart-in the literature (2–10) In addition to lymphedema secondary to mastectomy, this type
of angiosarcoma has also been described in areas of lymphedema secondary to a variety
of other mechanisms, including axillary node dissection for metastatic melanoma in
males (11), lymphedema of the abdominal wall following lymph node dissection for carcinoma of the penis (12), congenital lymphedema (3,4,13–16), lymphedema secondary
to a filarial infection (17–22), chronic idiopathic lymphedema (3,15,18,22–27), morbid obesity with lymphedema(28), and angiosarcoma complicating elephantiasis (29).
Angiosarcomas arising in areas of lymphedema have been designated rcomas on the presumption that the neoplasms originated from dilated lymphatic vessels.However, this assertion has not been definitively proved, and immunohistochemical andultrastructural studies support a hemangiomatous differentiation Therefore at this timethe term angiosarcoma is justified for neoplasms that develop in lymphedematous
lymphangiosa-areas (30).
More than 90% of all angiosarcomas associated with chronic lymphedema occur
following mastectomy for breast carcinoma (3) The mastectomy invariably includes
removal of the axillary lymph nodes, and in some patients, but not all, there is also theantecedent of adjuvant radiotherapy to the affected area The risk of developing angiosa-rcoma in postmastectomy patients who have a survival of 5 years or more is approxi-
mately 0.5% (19) The interval between the mastectomy and the development of
angiosarcoma ranges from 1 to 30 years The arm, most often the upper inner aspect, isthe most frequent site for early involvement Less commonly, the tumor appears moredistally, on the elbow or on the forearm In rare instances, postmastectomy angiosarcomahas been reported in patients who have experienced little or no lymphedema
C LINICAL F EATURES
Clinically, these lesions appear as bruise-like areas or violaceous nodules
superim-posed on the brownish nonpitting edema of the affected limb (31) (Fig 21) After the
appearance of the lesions, there is a rapid increase in their number and size, and they mayundergo ulceration In advanced cases, they spread distally to the hands and proximally
to the chest wall The clinical appearance and the histologic behavior of angiosarcomas
in lymphedematous extremities unassociated with mastectomy are essentially identical
to those of postmastectomy angiosarcoma
Angiosarcomas that originate in areas of chronic lymphedema exhibit similar
histo-pathologic features to those of angiosarcoma of the scalp and face (30,32) They appear
as irregular vascular spaces that form an intricate network of freely anastomosing vesselscontaining erythrocytes with extensive dissection of collagen Endothelial cell nuclei areplump and hyperchromatic Patchy lymphoid infiltrates are sometimes present around
Trang 2Fig 21 Cutaneous angiosarcoma associated with chronic postmastectomy lymphedema
(Stewart-Treves syndrome) (A) The entire upper extremity appears edematous, with multiple angiomatous nodules (B) In addition to the nodules, there are ill-delimited angiomatous plaques.
the newly formed vessels In some cases, there is a verrucous epidermal hyperplasia,
presumably caused by lymphedema and the involvement of the papillary dermis (33).
From a histogenetic point of view, the relationship between chronic lymphedema and
angiosarcoma is enigmatic Stewart and Treves, in their original report (1), postulated that unknown carcinogens within lymphatic fluid, acting in a locus minoris resistentia , induced the neoplastic change, a view that was also held by other authors (2) More
recently, it has been suggested that the lymphedema modifies the biochemical or
immu-nologic status of the affected limb fostering, the development of angiosarcoma (5,14).
The notion that areas with chronic lymphedema are “immunologically privileged sites”
is supported by the observation that skin grafts survive for long periods when they are
transferred to lymphedematous extremities (20,21).
Immunohistochemical studies in cutaneous angiosarcomas developing in
lymph-edematous extremities have documented positivity for factor VIII-related antigen (8,34),
and ultrastructural examination has demonstrated the presence of pericytes and
Weibel-Palade bodies in some cases (7,8,35,36) These special studies are useful in establishing
a differential diagnosis between Stewart-Treves angiosarcoma and metastatic breastcarcinoma in a lymphedematous arm, since both entities may show similar clinical andhistopathologic features In metastatic breast carcinoma, the neoplastic cells express
Trang 3immunoreactivity for cytokeratin owing to their epithelial nature, whereas factor
VIII-related antigen is negative (37).
Survival in angiosarcoma associated with lymphedema may be worse than in other
forms of cutaneous angiosarcoma Woodward et al (3) reported a mean survival time of
patients with angiosarcoma following mastectomy of 19 months, compared with 34
months for cutaneous angiosarcomas not related to lymphedema Sordillo et al (6)
reported a mean survival time of 31 months A longer survival time has been reported inpatients initially treated with radical surgery, including limb disarticulation, or hindquar-
ter or forequarter amputation (30) Other studies have found no significant difference in
survival when cases initially treated with wide excision were compared with those treated
with amputation (38).
References
1 Stewart FW, Treves N Lymphangiosarcoma in postmastectomy lymphedema Cancer 1948;1:64–81.
2 Herrmann JB Lymphangiosarcoma of the clinically edematous extremity Surg Gynecol Obstet 1965;121:1107–15.
3 Woodward AH, Ivins JC, Soule EH Lymphangiosarcoma arising in chronic lymphedematous ties Cancer 1972;30:562–72.
extremi-4 Taswell HF, Soule HE, Coventry MB Lymphangiosarcoma arising in chronic lymphedematous extremities J Bone Joint Surg 1962;44A:277–94.
5 Schreiber H, Barry FM, Russell WC, Macon WL IV, Ponsky JL, Pories WJ Stewart-Treves syndrome.
A lethal complication of postmastectomy lymphedema and regional immune deficiency Arch Surg 1979;114:82–5.
6 Sordillo PP, Chapman R, Hajdu DI, Magill GB, Golbey RB Lymphangiosarcoma Cancer 1981; 48:1674–9.
7 Silverberg SG, Kay S, Koss LG Postmastectomy lymphangiosarcoma: utrastructural observations Cancer 1971;27:100–8.
8 Kanitakis J, Bendalac A, Marchand C, et al Stewart-Treves syndrome: a histogenetic (ultrastructural and immunohistochemical) study J Cutan Pathol 1986;13:30–9.
9 Hultberg BM Angiosarcoma in chronically lymphedematous extremities: two cases of Stewart-Treves syndrome Am J Dermatopathol 1987;9:406–12.
10 Hildebrandt G, Mittag M, Gutz U, Kunze ML, Haustein UF Cutaneous breast angiosarcoma after conserving treatment of breast cancer Eur J Dermatol 2001;11:580–3.
11 Chen KTK, Bauer V, Flam MS Angiosarcoma in postsurgical lymphedema An unusual occurrence in
18 Alessi E, Sala F, Berti E Angiosarcomas in lymphedematous limbs Am J Dermatopathol 1986;8:371–8.
19 Shirger A Postoperative lymphedema: etiologic and diagnostic factors Med Clin North Am 1962;46:1045–50.
20 Stark RB, Dwyer EM, DeForest M Effect of surgical ablation of regional lymph nodes on survival of skin homographs Ann NY Acad Sci 1960;87:140–5.
Trang 421 Lambert PB, Frank HA, Bellman S, et al The role of the lymph trunks in the response to allogenic skin transplants Transplantation 1965;3:62–73.
22 Sordillo EM, Sordillo PP, Hadju SI, et al Lymphangiosarcoma after filarial infection J Dermatol Surg Oncol 1981;7:235–9.
23 Baes H Angiosarcoma in a chronic lymphedematous leg Dermatologica 1967;134:331–6.
24 Sinclair SA, Sviland L, Natarajan S Angiosarcoma arising in a chronically lymphoedematous leg Br
32 Cooper PH Angiosarcomas of the skin Semin Diagn Pathol 1987;4:2–17.
33 Diaz-Cascajo C, Weyers W, Borghi S, Reichel M Verrucous angiosarcoma of the skin: a distinct variant
of cutaneous angiosarcoma Histopathology 1998;32:556–61.
34 Capo V, Ozello L, Fenoglio CM, et al Angiosarcomas arising in edematous extremities Hum Pathol 1985;16:144–50.
35 McWilliam LJ, Harris M Histogenesis of postmastectomy angiosarcoma: an ultrastructural study Histopathology 1985;9:331–43.
36 Kindblom L-G, Stenman G, Angervall L Morphological and cytogenetic studies of angiosarcoma in Stewart-Treves syndrome Virchows Arch A Pathol Anat Histopathol 1991;419:439–45.
37 Hashimoto K, Hatsumoto M, Eto H, et al Differentiation of metastatic breast carcinoma from Treves angiosarcoma Arch Dermatol 1985;121:742–6.
Stewart-38 Grobmyer SR, Daly JM, Glotzbach RE, Grobmyer AJ Role of surgery in the management of postmastectomy extremity angiosarcoma (Stewart-Treves syndrome) J Surg Oncol 2000;73:1182–8.
Trang 58 RADIATION-INDUCED CUTANEOUS ANGIOSARCOMA
Postirradiation cutaneous angiosarcoma is a rare condition that has been describedfollowing the use of radiotherapy for the treatment of diverse conditions These include
cutaneous hemangiomas (1,2), acne (3), hand eczema (4), X-ray depilation for scalp ringworm during childhood (5), and malignant neoplasms such as carcinoma of the cervix (6–9), endometrium (10), ovary (11), and breast (12–26), Hodgkin’s disease (27), penile squamous cell carcinoma (28), or peripheral primitive neuroectodermal tumor (29) The ensuing angiosarcoma usually manifests after a long interval, ranging from 4
to 40 years (mean 23.3 years) when radiation therapy was administered for benign ditions, and from 4 to 25 years (mean 12.3 years), for patients in whom radiation therapywas used for malignant tumors These differences are probably related to the higherdosage and harder radiation in the group of patients with previous malignancy Preexist-
con-ing radiodermatitis of the involved area has been described in some cases (3,8,15,30,31).
C LINICAL F EATURES
The clinical appearance of postirradiation cutaneous angiosarcoma varies from case
to case Diffuse infiltrative plaques (Fig 22), papulo-nodules, and ulcerated lesions havebeen described All lesions occurred in the area of irradiation or its immediate vicinity,and because most of the cases appeared following radiation for breast and genitourinarymalignant tumors, the chest wall and the lower abdominal wall are the sites most fre-quently involved by postirradiation angiosarcomas Most of these patients had no evi-dence of lymphedema, suggesting that radiation is the most important etiologic factor
H ISTOPATHOLOGIC F EATURES
Postirradiation angiosarcoma shows a histopathologic picture similar to that of othervariants of cutaneous angiosarcoma (Fig 23) In early lesions, neoplastic vessels infil-trate collagen bundles of the entire thickness of the dermis and often extend to thesubcutaneous tissue The endothelial cells lining these vessels show variable atypia, but
at least some have large hyperchromatic nuclei and protrude into the lumina of theirregular vascular channels Sometimes papillations lined by protuberant endothelialcells are present As the lesions become increasingly cellular, aggregations of epithelioidneoplastic cells develop In these aggregations, vacuoles within the cytoplasm of neo-plastic cells are seen as an expression of primitive luminal differentiation Mitotic figuresare frequently seen in the solid-appearing zones A frequent finding is the presence oflymphoid nodules in both the superficial and deep areas of the dermis In the advancingedges of these solid areas there are jagged vessels similar to those seen in earlier lesionsinfiltrating between collagen bundles of the dermis
Cutaneous angiosarcoma originating in irradiated areas of the skin should be guished histopathologically from the benign vascular proliferations arising in irradiated
distin-skin (see Chapter 8, Subheading 15.), which have received different names in the ture, including lymphangiectases (32), benign lymphangiomatous papules (33), lym- phangioma (34–44), atypical vascular lesions (45), benign lymphangioendothelioma (46), or benign vascular proliferations in irradiated skin (47) Histopathologically, they
litera-consist of relatively well-circumscribed vascular proliferations involving the dermis,without extension to the subcutaneous fat, and they do not involve the epidermis Mostlesions show irregular dilated vascular spaces, with a branching and anastomosing pat-tern, and a lymphatic appearance in the superficial dermis A discontinuous single layer
Trang 6Fig 22 (A) Angiosarcoma of the breast appeared after radiation for breast carcinoma (B) Close-up
view showing the angiomatous appearance of the plaques of angiosarcoma.
of endothelial cells with spindled or flattened nuclei lines the vascular channels, and theirlumina appear empty In many areas, adjacent vascular channels show a “back-to-back”arrangement, with the two vascular lumina only separated by a thin layer of endothelialcells Numerous small papillary projections, also lined by a single layer of endothelialcells, are seen projecting into the lumina of the dilated lymphatic vessels The stroma ofthe lesions consists of fibrillary collagen and numerous spindled or stellate fibroblasts
Trang 8In some cases, dense nodular infiltrates of lymphocytes with germinal centers are present
in the vicinity of the dilated vascular channels
Furthermore, in contrast to well-differentiated angiosarcomas, benign vascular erations in irradiated skin do not involve the subcutaneous tissue, and there is no substan-tial cytologic atypia because the nuclei of endothelial cells lining the vascular channelsare monomorphous, with inconspicuous nucleoli and no mitotic figures In contrast,angiosarcomas may present with multiple layers of atypical endothelial cells lining ir-regular vascular and anastomosing channels, the so-called piling-up phenomenon; this isnot seen in atypical vascular proliferations in irradiated skin
In general, the prognosis for angiosarcoma originating in irradiated areas is poor (6),
although there are cases of radiation-induced low-grade cutaneous angiosarcomas with
multiple recurrences However, they did not produce metastasis (11) Treatment consists
of radical surgery with wide margins of noninvolved tissue The neoplasm usually extendsfar beyond the clinically visible boundaries of the lesion, and metastases have alreadydeveloped by the time surgery is performed
References
1 Caldwell JB, Ryan MT, Benson PM, James WD Cutaneous angiosarcoma arising in the radiation site
of a congenital hemangioma J Am Acad Dermatol 1995;33:865–70.
2 Cabo H, Cohen ES, Casas GJ, Allevato M, Woscoff A Cutaneous angiosarcoma arising on the radiation site of a congenital facial hemangioma Int J Dermatol 1998;37:638–9.
3 Seo IS, Warner TFCS, Warren JS, Bennett JF Cutaneous postirradiation sarcoma Ultrastructural dence of pluripotential mesenchymal cell derivation Cancer 1985;56:761–7.
evi-4 Girard C, Johnson WC, Graham JH Cutaneous angiosarcoma Cancer 1970;26:868–83.
5 Stone NM, Holden CA Postirradiation angiosarcoma Clin Exp Dermatol 1997;22:46–7.
6 Goette EK, Detlefs RL Postirradiation angiosarcoma J Am Acad Dermatol 1985;12:922–6.
7 Maddox JC, Evans HL Angiosarcoma of skin and soft tissue A study of forty-four cases Cancer 1981;48:1907–21.
8 Krasagakis K, Hettmannsperger U, Tebbe B, Garbe C Cutaneous metastatic angiosarcoma with a lethal outcome, following radiotherapy for a cervical carcinoma Br J Dermatol 1995;133:610–4.
9 Kim MK, Huh SJ, Kim DY, et al Secondary angiosarcoma following irradiation—case report and review of the literature Radiat Med 1998;16:55–60.
10 Paik HH, Komorowski R Hemangiosarcoma of the abdominal wall following irradiation therapy of endometrial carcinoma Am J Clin Pathol 1976;66:810–4.
11 Chen TK, Goffman KD, Hendricks EJ Angiosarcoma following therapeutic irradiation Cancer 1979;44:2044–8.
12 Edeiken S, Russo DP, Knecht J, et al Angiosarcoma after tylectomy and radiation therapy for carcinoma
of the breast Cancer 1992;70:644–7.
13 Rubin E, Maddox WA, Mazur MT Cutaneous angiosarcoma of the breast 7 years after lumpectomy and radiation therapy Radiology 1990;174:258–60.
14 Sessions SC, Smenk RD Cutaneous angiosarcoma of the breast after segmental mastectomy and tion therapy Arch Surg 1992;127:1362–3.
radia-15 Stokkel MPM, Peterse HL Angiosarcoma of the breast after lumpectomy and radiation therapy for adenocarcinoma Cancer 1992;69:2965–8.
Fig 23 (Opposite page) Histopathologic features of postirradiation angiosarcoma of the breast.
(A) Scanning power shows dense cellular aggregates at the superficial dermis (B) Higher
magnification demonstrates that these cellular aggregates are surrounding elongated, slit-like
vascular spaces (C) Still higher magnification shows that neoplastic cells are pleomorphic, with
hyperchromatic nuclei and numerous mitotic figures.
Trang 916 Moskaluk CA, Merino MJ, Danforth DN, Medeiros LJ Low-grade angiosarcoma of the skin of the breast: a complication of lumpectomy and radiation therapy for breast carcinoma Hum Pathol 1992;23:710–4.
17 Bolin DJ, Lukas GM Low-grade dermal angiosarcoma of the breast following radiotherapy Am Surg 1996;62:668–72.
18 Autio P, Kariniemi AL Angiosarcoma A rare secondary malignancy after breast cancer treatment Eur
J Dermatol 1999;9:118–21.
19 Majeski J, Austin RM, Fitzgerald RH Cutaneous angiosarcoma in an irradiated breast after breast conservation therapy for cancer: association with chronic breast lymphedema J Surg Oncol 2000;74:208–12.
20 Cafiero EF, Gipponi M, Peressini A, et al Radiation-associated angiosarcoma: diagnostic and tic implications: two cases reports and review of the literature Cancer 1996;77:2496–502.
therapeu-21 Cancellieri A, Eusebi V, Mambellin V, et al Well-differentiated angiosarcoma of the skin following radiotherapy Pathol Res Pract 1991;187:301–6.
22 Givens SS, Ellerbroek NA, Butler JJ, et al Angiosarcoma arising in an irradiated breast: a case report and review of the literature Cancer 1989;64:2214–6.
23 Marchal C, Weber B, de Lafontan B Nine breast angiosarcomas after conservative treatment for breast carcinoma: a survey from French comprehensive cancer centers Int J Radiat Oncol Biol Phys 1999;44:113–9.
24 Otis CN, Peschel R, McKhann C et al The rapid onset of cutaneous angiosarcoma after radiotherapy for breast cancer Cancer 1986;57:2130–4.
25 Parham DM, Fisher C Angiosarcomas of the breast developing post radiotherapy Histopathology 1997;31:189–95.
26 Shaikh NA, Beaconsfield T, Walker M, et al Postirradiation angiosarcoma of the breast: a case report Eur J Surg Oncol 1988;14:449–51.
27 Richards PG, Bessell EM, Goolden AWG Spinal extradural angiosarcoma occurring after treatment for Hodgkin’s disease Clin Oncol 1983;9:165–8.
28 Prescott RJ, Mainwaring AR Irradiation-induced penile angiosarcoma Postgrad Med J 1990;66:576–9.
29 Coffin CM, Vietti TJ, Land VJ, et al Cutaneous angiosarcoma as a second malignant neoplasm after peripheral primitive neuroectodermal tumor Med Pediatr Oncol 1992;20:352–6.
30 Hodgkinson DJ, Soule EH, Woods JE Cutaneous angiosarcoma of the head and neck Cancer 1979;44:1106–13.
31 Calnan J, Cowdell RH Lymphangioendothelioma of the anterior abdominal wall: report of a case Br J Surg 1959;46:375–9.
32 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.
33 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.
34 Fisher I, Orkin M Acquired lymphangioma (lymphangiectasis) Arch Dermatol 1970;101:230–4.
35 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.
36 Handfield-Jones SE, Prendville WJ, Norman S Vulval lymphangiectasia Genitourin Med 1989;65:335–7.
37 Harwood CA, Mortimer PS Acquired vulvar lymphangiomata mimicking genital warts Br J Dermatol 1993;129:334–6.
38 Kennedy CTC Lymphangiectasia of the vulva following hysterectomy and radiotherapy Br J Dermatol 1990;123(suppl 37):92–3.
39 Kurwa A, Waddinton E Post mastectomy lymphangiomatosis Br J Dermatol 1968;80:840.
40 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.
41 Leshin B, Whitaker D, Foucar E Lymphangioma circumscriptum following mastectomy and radiation therapy J Am Acad Dermatol 1986;15:1117–9.
42 Plotnick H, Richfield D Tuberous lymphangiectatic varices secondary to radical mastectomy Arch Dermatol Syphilol 1956;74:466–8.
43 Prioleau PG, Santa Cruz DJ Lymphangioma circumscriptum following radical mastectomy and tion therapy Cancer 1978;42:1989–91.
Trang 10radia-44 Young AW Jr, Wind RM, Tovell HM Lymphangioma of vulva: acquired following treatment for cervical cancer NY State J Med 1980;80:987–9.
45 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.
46 Rosso R, Gianelli U, Carnevali L Acquired progressive lymphangioma of the skin following therapy for breast carcinoma J Cutan Pathol 1995;22:164–7.
radio-47 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.
Trang 119 EPITHELIOID ANGIOSARCOMA
C LINICAL F EATURES
This is a rare variant of the cutaneous angiosarcoma recently described (1–7)
Clini-cally, lesions of cutaneous epithelioid angiosarcoma are indistinguishable from tional angiosarcoma (Fig 24) Perhaps the preferential location of these lesions on thelower extremities is the only distinctive clinical feature, although lesions on the scalp and
conven-face have also been described (1,5) Radiation exposure (3), a reaction to a foreign body (7), and chronic immunosuppression in the setting of renal transplantation (8) have been
implicated as possible causes
H ISTOPATHOLOGIC F EATURES
Histopathologically, cutaneous epithelioid angiosarcoma mimics an epithelial plasm The tumor is composed of sheets of rounded epithelioid cells with a large cyto-plasm, vesicular nuclei, and prominent nucleoli (Fig 25) Areas of irregular vascularchannels lined by atypical endothelial cells that dissect the collagen bundles are notprominent, but the finding of such areas has high diagnostic value In some areas, epithe-lioid cells exhibit cytoplasmic vacuoles as an expression of primitive luminal differen-tiation Immunohistochemistry corroborates the vascular nature of this epithelioid
neo-neoplasm because expression of factor VIII-related antigen, Ulex europaeus I lectin,
CD31, and CD34 have been documented in examples of cutaneous epithelioid
angiosa-rcoma (1–5) However, these tumors also consistently express cytokeratins (3–6,9),
attributable to the abundance of intracytoplasmic intermediate filaments in neoplasticcells, and this phenomenon may result in the misinterpretation of this type of angiosar-coma as carcinoma Ultrastructural studies have documented a prominent cytoskeleton
of intermediate filaments, numerous pinocytotic vesicles, and scarce (1,3) or no (2,5,7)
Weibel-Palade bodies in neoplastic cells of cutaneous epithelioid angiosarcoma
Fig 24 Clinical features of epithelioid angiosarcoma Erythematous nodules with angiomatous
appearance.
Fig 25 (Opposite page) Histopathologic features of epithelioid angiosarcoma (A) Low power
shows a cellular proliferation involving the entire dermis (B) Higher magnification demonstrates solid aggregations of neoplastic cells with some inconspicuous vascular lumina (C) Still higher
magnification demonstrates that neoplastic cells have an epithelioid appearance, and many of them exhibit prominent vacuolization of their cytoplasm as an expression of primitive luminal differentiation.
Trang 13T REATMENT
Wide surgical excision of the neoplasm is necessary Despite claims of a better
prog-nosis for this variant of cutaneous angiosarcoma (2), these have a highly aggressive
course, and most of the patients develop widespread metastatic disease within a year of
3 Fletcher CDM, Beham A, Bekir S, Clarke AMT, Marley NJE Epithelioid angiosarcoma of deep soft tissue:
a distinctive tumor readily mistaken for an epithelial neoplasm Am J Surg Pathol 1991;15:915–24.
4 Maiorana A, Fante R, Fano RA, Collina G Epithelioid angiosarcoma of the buttock Case report with immunohistochemical study on the expression of keratin polypeptides Surg Pathol 1991;4:325–32.
5 Prescott RJ, Banerjee SS, Eyden BP, Haboubi NY Cutaneous epithelioid angiosarcoma: a logical study of four cases Histopathology 1994;25:421–9.
clinicopatho-6 McCluggage WG, Clarke R, Toner PG Cutaneous epithelioid angiosarcoma exhibiting cytokeratin positivity Histopathology 1995;27:291–4.
7 Jennings TA, Peterson L, Axiotis CA, Friedlaender GE, Cooke RA, Rosai J Angiosarcoma associated with foreign body material Cancer 1988; 62:2436–44.
8 Wehrli BM, Janzen DL, Shokeir O, Masri BA, Byrne SK, O’Connell JX Epithelioid angiosarcoma arising in a surgically constructed arteriovenous fistula: a rare complication of chronic immuno- ssuppression in the setting of renal transplantation Am J Surg Pathol 1998;22:1154–9.
9 Ng WK, Collins RJ, Law D, Gwi E Cutaneous epithelioid angiosarcoma: a potential diagnostic trap for cytopathologists Diagn Cytopathol 1997;16:160–6.
Trang 1410 MALIGNANT GLOMUS TUMOR (GLOMANGIOSARCOMA)
Glomangiosarcomas are exceptionally rare, to the point that some authors doubt theirexistence The most controversial issue is the recognition and acceptance of malignantglomus tumors in which no benign component is present In the literature there are only
a few reports of this neoplasm (1–14) The first report of a malignant variety of glomus tumor (MGT) was by Lumley and Stansfeld in 1972 (1) A year later, Anagnostou et al (15)
identified 1 MGT in a series of 20 subcutaneous glomus tumors studied In most instances,there was no recurrence of the tumor, and the few recurrences were usually classified as
locally infiltrating glomus tumors with indistinct capsular borders (4,5,7).
C LINICAL F EATURES
The lesions of glomangiosarcomas are larger and deeper than conventional glomustumors, and they are predominantly located on the extremities, where they appear as
subcutaneous masses The tumors affect men and women equally (12) Metastatic disease
has been documented in only 10 cases of histopathologically defined MGT, and in 8 ofthese patients, death was a consequence of the widespread metastases from the
glomangiosarcoma (6,10,12) Locally aggressive behavior appears to be more common
in these neoplasms
H ISTOPATHOLOGIC F EATURES
There are three proposed categories for malignant glomus tumors: (1) locally tive glomus tumor—these are neoplasms that lack atypical features but show locallyaggressive behavior (LIGT); (2) glomangiosarcomas that result from the transformation
infiltra-of a glomus tumor (GABG)—these are the most common type infiltra-of MGT, and remainingareas of typical GT can be identified (Fig 26); and (3) de novo glomangiosarcoma
(GADN), the most unusual form of MGT (4).
In the second group, there are sarcomatous areas intermingled with areas of benignglomus tumor In these cases it is important to identify the benign component, as it is themost important clue to the diagnosis of glomangiosarcoma The malignant areas appear
as poorly circumscribed and infiltrative neoplasms composed of fascicles of spindle cells
or aggregations of round glomoid cells with nuclear pleomorphism, frequent mitotic
figures, and foci of necrosis en masse In some neoplasms, there is a peculiar arrangement
of neoplastic cells, with small round glomus cells at the periphery and central areas of
spindle cells (12) A diagnosis of glomangiosarcoma should be not misconstructed in
cases of long-standing glomus tumors, in which it is possible to see glomus cells withlarge hyperchromatic nuclei, probably as result of degenerative changes similar to thoseseen in ancient schwannoma Some authors have proposed the name symplastic glomus
tumor for these benign glomus tumors with nuclear atypia (12).
In the absence of the benign glomus tumor component, the diagnosis of sarcoma nearly always presupposes the use of immunohistochemistry Immunohis-tochemical studies in cases of glomangiosarcoma have demonstrated immunoreactivity
glomangio-of neoplastic cells for vimentin, collagen type IV, muscle-specific actin, and smoothmuscle actin, whereas neuron-specific enolase, desmin, Leu-7, CD34, and S-100 protein
positivities are detected focally in only some cases (2,12) Some neoplastic cells express caldesmon and calponin (12) Factor VIII-related antigen was negative in neoplastic cells (3) In one example of a glomangiosarcoma derived from a benign glomus tumor, immu-
nohistochemical studies demonstrated that bcl-2, an inhibitor of apoptosis, was strongly
Trang 16expressed in the glomangiosarcoma areas, with only weak staining in the benign areas.The proliferation index of glomangiosarcoma was almost 10-fold higher than that of thebenign glomus tumor Numerous nuclei of glomangiosarcoma were intensely stained for
the tumor suppressor protein p53 (11) Ultrastructural studies (2,3) have demonstrated
that neoplastic cells of glomangiosarcoma show prominent nucleoli, poorly developedorganelles, and some bundles of tonofilaments Micropinocytotic vesicles have also been
identified in some cases (3).
Histopathologically the differential diagnosis of glomangiosarcoma includes nodularhidradenoma, leiomyosarcoma, and hemangiopericytoma Nodular hidradenomas areneoplasms with sweat gland differentiation that are usually well circumscribed Leiomyo-sarcomas are usually poorly circumscribed, large, asymmetrical neoplasms with muscledifferentiation Hemangiopericytomas are composed of branching vessels of variablesize and shape, which give the neoplasm a characteristic “staghorn” configuration
Complete removal by surgical excision is essential if local recurrence and eventualmetastasis are to be avoided Wide excision of the lesion has been found to be adequatetherapy
References
1 Lumley JSP, Stansfeld AG Infiltrating glomus tumour of lower limb BMJ 1972;1:484–5.
2 Aiba M, Hirayama A, Kuramochi S Glomangiosarcoma in a glomus tumor An immunohistochemical and ultrastructural study Cancer 1988;61:1467–71.
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Fig 26 Malignant glomus tumor (glomangiosarcoma) (A) Low-power magnification shows a
large, asymmetric neoplasm involving the entire dermis (B) The superficial part of the neoplasm reveals vascular structures of a glomus tumor (C) Other areas of the neoplasm demonstrate a cellular neoplasm, composed of cuboidal cells with some degree of nuclear pleomorphism (D) At
this power there are necrotic cells and an increased number of mitotic figures.
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