Australasian Journal of Dermatology

(2003)

44

,

273–276

Correspondence: Dr Stuart Murray, Department of Dermatology,Flinders Medical Centre, Bedford Park, SA 5042, Australia.

Stuart Murray, BM BS. Ivan Simmons, FACD. Craig James, FRCPA.Submitted 20 November 2002; accepted 1 May 2003.

CASE REPORT

Cutaneous angiosarcoma of the face and scalp presenting as alopecia

Stuart Murray,

1

Ivan Simmons

1

and Craig James

2

1

Department of Dermatology, Royal Adelaide Hospital,

2

Adelaide Pathology Partners, Adelaide, South Australia, Australia

INTRODUCTION

Angiosarcoma is a malignant tumour arising from vascularor lymphatic endothelium. It is a rare tumour comprisingabout 2% of soft-tissue sarcomas.

1

Cutaneous angiosarcomasoccur predominantly in male (2:1), elderly patients, withmore than 50% occurring in the scalp or forehead.

2

Clinicalpresentation varies widely but there has been only onereport of angiosarcoma presenting as scarring alopecia.

3

The following case is reported as it highlights the unusualfeature of angiosarcoma presenting with an initial clinicalsign of alopecia.

CASE REPORT

An 83-year-old woman presented with a 6-month history ofhair loss involving the bilateral parietal scalp with associated‘bruising’ and purplish discoloration of the skin involvingher forehead. More recently, she had developed a nodularmass in the region of her posterior scalp. There was noassociated pain and she was otherwise well. No familyhistory of androgenetic alopecia was evident.

Examination revealed diffuse hair loss involving herbilateral parieto-temporal scalp, with areas of localizedscarring and with obliteration of follicular orifices. Thefrontal hair line was preserved. There were purpuric, viola-ceous patches involving her bilateral forehead and peri-orbital region and an indurated angiomatous mass involvingher right parieto-occipital scalp (Fig. 1). The hair loss wasmore prominent in the areas of infiltration. There was nolymphadenopathy or signs of androgenization.

Skin biopsies of the scalp and forehead demonstrated amoderately differentiated angiosarcoma (grade 2 or 3)extending through the dermis into the subcutis. The tumourcomprised irregular serpiginous focally fused vascularchannels, some filled with erythrocytes while others wereempty and more lymphatic type in appearance. The vesselswere lined by plump, hyperchromatic atypical endothelialcells. The tumour dissected between the adnexal structures,with associated dermal haemorrhage and a patchy lympho-cytic inflammatory infiltrate (Figs 2,3). There were foci oftumour necrosis and perineural spread as well as some solidepithelioid growth areas.

The parietal scalp biopsy (Fig. 4) demonstrated a signifi-cant increase in miniaturized telogen hair follicles in areasof tumour growth and focal-tumour-associated scarring hairloss. While there was some scarring, the predominantpattern was one of follicular miniaturization. No peribulbarinflammatory infiltrates or dramatically altered catagen/telogen to anagen follicle ratio were evident.

CD31, CD34, factor VIII and vimentin-positive immuno-cytochemistry confirmed the endothelial nature of themalignant neoplasm. CD34 outlined neoplastic vascular

SUMMARY

An 83-year-old woman presented with a 6-monthhistory of hair loss and painless bruising involvingher forehead and scalp. She was otherwise well. Skinbiopsy of her scalp confirmed angiosarcoma with asignificant increase in miniaturized and telogen hairfollicles and some tumour-associated scarring hairloss. She was commenced on the chemotherapeuticagent paclitaxel and then subsequently the semi-synthetic taxane docetaxol. Treatment was terminatedbecause of lack of response and adverse effects.Alopecia is an uncommon presentation in angio-sarcoma and in this case there was a mixed pattern offocal scarring and follicular miniaturization. The latterwas present only in areas of tumour involvement andnot in a typical pattern distribution for androgeneticalopecia.The direct role of tumour in follicular miniaturizationand alopecia is speculated and the implications of thisfor novel future treatment strategies is discussed.

Key words: alopecia neoplastica, androgeneticalopecia, docetaxol, follicular miniaturization,paclitaxel, scarring alopecia, steroid receptors.

274 S Murray

et al.

channels, but was negative in the solid areas. No cytokeratinreactivity was evident. Immunocytochemistry for oestrogen,progesterone and androgen receptors failed to demonstratetumour cell staining.

Computed tomography head scan demonstrated soft-tissueswelling overlying the right parieto-occipital scalp. Theunderlying skull vault was not eroded. Baseline blood

investigations are listed in Table 1. The elevated erythrocytesedimentation rate is consistent with the underlying neo-plastic disease.

In this case, surgery was not an option because of theextensive disease and the patient was commenced on thechemotherapeutic agent paclitaxel. This was complicated bya severe hypersensitivity reaction with extensive urticariaand mild hypotension. She was subsequently commenced onthe semi-synthetic taxane docetaxel for a period of 7 weeks.Treatment was ceased because of lack of response andasthenia. The patient’s condition deteriorated rapidly andshe subsequently died.

Figure 1

Right parieto-occipital scalp: multiple foci of induratedareas of angiosarcoma.

Figure 2

Right forehead biopsy: moderately differentiated angio-sarcoma extending through the dermis, with irregular serpiginousfocally fused vascular channels. Patchy lymphocytic infiltrate withsome dermal haemorrhage (H&E).

Figure 3

Right forehead biopsy: irregular outlined vascularchannels, lined by atypical endothelial cells showing piling upchange and focal intraluminal papillary projections (H&E).

Figure 4

Right parietal scalp biopsy: Area of alopecia with angio-sarcoma revealing (1) focal scarring, (2) follicular miniaturizationand (3) telogen hair follicles (H&E).

Angiosarcoma of the scalp and alopecia 275

DISCUSSION

Cutaneous angiosarcoma is an uncommon, malignanttumour and clinical awareness of this neoplasm remainslow. Angiosarcoma has only once been reported presentingwith alopecia.

3

The unusual feature of this case was the significantalopecia in the region of the parietal scalp. The biopsyshowed a marked increase in miniaturized and telogen hairfollicles, with some tumour-associated scarring hair loss.Focal scarring was present where there was extensivedermal involvement with neoplastic tissue, which was con-sistent with the previously reported case.

3

This resulted indestruction of adnexal structures including hair follicles. Thepredominant histological and clinical pattern, however, wasa miniaturizing hair loss pattern reminiscent of that seen inandrogenetic type alopecia. There was no peribulbar inflam-mation or altered anagen to catagen/telogen ratio as seen inactive alopecia areata. Other rare causes of follicularminiaturization, including congenital triangular alopeciaand alopecia associated with pachyonychia congenita,

4

wereexcluded clinically.

The hair loss had only been noted over the preceding6 months, raising the differential diagnosis of whether theangiosarcoma of the scalp was occurring in a patient withbackground androgenetic alopecia or whether the tumourwas directly inducing follicular miniaturization and hairloss. Given that the violaceous areas corresponded to theareas of hair loss and that the pattern of hair loss was nottypical of androgenetic alopecia, the authors speculate thatthe tumour directly induced follicular miniaturization and araised telogen count. In the previous case report of scarringalopecia with angiosarcoma there is no specific mention offollicular miniaturization.

3

The exact aetiology of the hair loss in this case is difficultto ascertain. Oestrogen, progesterone and glucocorticoidreceptors have been demonstrated in breast angiosarcoma,

5,6

although the authors failed to demonstrate positive immuno-cytochemistry for oestrogen, progesterone or androgenreceptors on formalin-fixed tumour tissue. It is worth specu-lating, however, whether the hair loss that developed rapidlyover a 6-month period related to the tumour by a direct effector possibly by androgenic or other hormonal stimuli. Thehair loss developing in our case raises the possibility thathormonal manipulation could have a theoretical rolein the treatment of angiosarcoma, a tumour with a currentlydismal prognosis.

Angiosarcomas are often multifocal lesions that are notalways clinically evident and are typically painless. Theymay simulate infective and inflammatory disorders, all con-tributing to a delayed diagnosis. Early biopsy is essential todetect the neoplasm at a stage when more effective treatmentis feasible. Alopecia neoplastica has been reported in associ-ation with both primary and secondary tumours, with thescalp being a relatively common site of cutaneous metastasessecondary to breast

7

and gastric

8

carcinoma.There is no well-defined approach to treatment. For small

focal lesions, surgical resection followed by wide field radi-ation therapy is recommended; however, because of theextensive disease in this patient, this was not an option.Chemotherapeutic agents have been used including paclit-axel and the semi-synthetic taxane docetaxol. These agentshave both antiangiogenic and apoptotic induction effects

9

and have been shown to selectively inhibit the proliferationof endothelial cells.

10

Hypersensitivity reactions have been reported to occur in4% of patients upon first exposure to paclitaxel, as was thecase in our patient.

11

Their efficacy in angiosarcoma isundefined, with some studies reporting improved survivalwhile others suggest no survival benefit.

12–14

We have presented a patient with hair loss as a result of anunderlying cutaneous angiosarcoma in order to increase theawareness of the rare entity of alopecia neoplastica, therecognition of which may lead to identification of this poorprognostic tumour at an earlier stage.

REFERENCES

1. Mackie R. Soft tissue tumours. In: Champion RH, Burton JL,Burns DA, Breathnach SM (eds).

Textbook of Dermatology

,Vol. 3, 6th edn. Oxford: Blackwell Science, 1998; 2347–72.

2. Holden CA, Spittle MJ, Wilson Jones EW. Angiosarcoma of theface

and

scalp.

Prognosis

and

treatment.

Cancer

1987;

59

:1046–57.

3. Knight TE, Robinson HM, Sina B. Angiosarcoma (angioendo-thelioma) of the scalp. An unusual case of scarring alopecia.

Arch. Dermatol.

1980;

116

: 683–6.4. Templeton SF, Wiegand SE. Pachyonychia congenita-associated

alopecia. A microscopic analysis using transverse section tech-nique.

Am. J. Dermatopathol.

1997;

19

: 180–4.5. Brentani M, Pacheo M, Oshima T, Nagai M, Lemos B, Goes S.

Steroid receptors in breast angiosarcoma.

Cancer

1983;

51

:2105–11.

6. Singh Y, Inque K, Kawanashi H, Hioki K, Homo T, Shikala N.Angiosarcoma of the breast: Immunohistochemical demon-stration of steroid receptors and literature review.

Breast Cancer

1996;

3

: 125–9.7. Carson HJ, Pellettiere EV, Lack E. Alopecia neoplastica simu-

lating alopecia areata and antedating the detection of primarybreast carcinoma.

J. Cutan. Pathol.

1994;

1

: 67–70.8. Kim HJ, Min HG, Lee ES. Alopecia neoplastica in a patient with

gastric carcinoma.

Br. J. Dermatol.

1999;

6

: 1122–4.9. Belotti D, Vergani V, Drudis T. The micro-tubule affecting drug

paclitaxel has anti-angiogenic activity.

Clin. Cancer Res.

1996;

2

:1843–9.

10. Wang

J,

Iou

P,

Lesniewski

R,

Henkin

J.

Paclitaxel

at

ultralow concentrations inhibits angiogenesis without affectingcellular

microtubule

assembly.

Anticancer

Drugs

2003;

14

:13–19.

Table 1

Blood tests

Test Result Normal range

Haemoglobin 10.9 g/dL 11.5–15.5 g/dLMean cell volume 88.5 fL 80–95 fLPlatelets 220

�

10

9

/L 150–400

�

10

9

/LErythrocyte sedimentation rate 101 mm/hour 5–15 mm/hourElectrolytes NormalUrea/creatinine NormalGamma glutamyltransferase 63 U/L <45 U/L

276 S Murray

et al.

11. Quock J, Dea G, Tanaka M, Gandara D, Lara P, Lau D. Pre-medication strategy for weekly paclitaxel.

Cancer Invest.

2002;

20

: 666–72.12. Casper ES, Waltzman RJ, Schartz GK, Sugarman A, Pfister D,

Ilson D. Phase II trial of paclitaxel in patients with soft tissuesarcoma.

Cancer Invest.

1998;

16

: 442–6.

13. Fata

F,

O’Reilly

E,

Ilson

D,

Pfister

D,

Leffel

D,

Kelson

D,Schartz G, Casper ES. Paclitaxel in the treatment of patients withangiosarcoma of the scalp or face.

Cancer

1999;

86

: 2034–7.14. Naka N, Oksawa M, Tomita Y. Prognostic factors in angio-

sarcoma: A multivariate analysis of 55 cases.

J. Surg. Oncol.

1996;

61

: 170–6.