The Journal of Laryngology and Otology May 1979. Vol. 93. pp. 477-494.
Haemangiopericytoma in otolaryngology By ROGER GUDRUN
Introduction HAEMANGIOPERICYTOMA is a rare vascular tumour. Since 1942, it has fascinated pathologists as well as clinicians by its unpredictable and variable biological behaviour. Kauffman and Stout (1960) called it an exasperating tumour. In 1942, Stout and Murray used the term 'haemangiopericytoma' for the first time and, after prolonged tissue culture studies, recognized it as a pathological entity. They presented nine patients with this tumour one of whom could be considered as the first case ever reported in Otolaryngology. He was a male adult patient of 31 with a pedunculated lesion of the infra-auricular region. In 1949, Stout published his second series which included 25 cases of haemangiopericytoma: Case No. 4 with an oropharyngeal lesion (base of the tongue), and Case No. 11 with the first nasal haemangiopericytoma. Walike and Bailey (1971) reported the first case of haemangiopericytoma of the larynx in a female patient, 64 years old, with gross chronic pemphigus vulgaris who developed stridor secondary to a nodular bosselated lesion of the epiglottis. The tumour arises from proliferation of special cells called 'Pericytes' which are found outside the capillaries. Hence, it can arise anywhere in the body. Diagnosis of the tumour is not possible clinically and sometimes even histologically. Consequently, there is always some indecisiveness regarding the management of these tumours. In the present paper a case of nasal haemangiopericytoma is reported, to be added to the previous fourteen cases in the literature. The evolution and ultrastructure of the tumour is described in addition to an outline of the modes of treatment which may be adopted when confronted with this unusual vascular tumour. Case report A.K., a 61-year-old white male, was referred by his family doctor to the E.N.T. department of St. Thomas' Hospital, London, on 15 December 1976, with six months' history of right-sided nasal obstruction. He had one spell of epistaxis three weeks prior to his visit. He also noticed slow painless bulging of the right eye. His past medical history, apart from appendicectomy in 1946, did not reveal any significant information. 477
478
R. GUDRUN
FIG. 1 Large soft-tissue mass occupying the right nasal cavity. Right antrum seems opaque.
FIG. 2 Tomogram of the paranasal sinuses. No definite bone erosion of the orbit or anterior cranial fosa.
HAEMANGIOPERICYTOMA IN OTOLARYNGOLOGY
479
Clinically, he had right proptosis without any visual defect. There was obvious external widening of the nose. The right nasal cavity was filled almost completely with a greyish polypoid mass pushing the nasal septum to the left. The post-nasal space showed the same mass protruding from the posterior choana. The rest of his upper food and air passages did not reveal any gross abnormality. There were no palpable lymph nodes in the neck. X-ray of the para-nasal sinuses showed an opaque right antrum with possible erosion of its medial wall (Fig. 1). Tomograms did not indicate any bone destruction in relation to the orbit and anterior cranial fossa (Fig. 2). No abnormality was found in the blood or chest X-ray. On 31 December 1976, the patient was admitted to hospital for examination under general anaesthesia and biopsy. The latter caused a blood loss of 800 ml., due to the vascularity of the tumour. Histological diagnosis was: malignant haemangiopericytoma (Figs. 3, 4 and 5). On 21 January 1977, through a right lateral rhinotomy incision, the tumour was found to arise from the right ethmoid region. It had eroded the medial wall of the orbit in places but the orbital periosteum was intact. It extended superiorly into the right frontal sinus but, on removal, the sinus wall appeared norrnal. The left sinus contained some pus but no tumour. There was a defect in the anterior cranial fossa and the dura seemed to be involved. Oedematous antral mucosa was stripped off. The sinus itself appeared free of the lesion. The naso-antral cavity was packed with BIPP, and the wound closed in two layers. Blood loss throughout the excision was one unit which was replaced. The mass removed measured roughly 5 x 4 x 3 cm. in size, and the histological
FIG. 3 Large number of round and spindle-shaped cells are seen to surround the vascular lumina. (H. & E., X400).
480
R. GUDRUN
FIG. 4 Multiple vascular spaces with sharply demarcated reticulin sheaths. (Laidlaw's Silver stain x 100).
FIG. 5 Silver impregnation showing the perivascular arrangement of the pericytes. (Laidlaw's stain x400).
;
HAEMANGIOPERICYTOMA IN OTOLARYNGOLOGY
481
sections confirmed the pre-operative diagnosis of malignant haemangiopericytoma. Therefore, it was decided to follow the surgical excision by a course of radiotherapy. On 7 February 1977, Cobalt 60 teletherapy, planned with two wedges aiming at 5,500 r in 12 treatments over 28 days to the right side of the face, was commenced. The patient, after completion of his treatment, was assessed regularly by both E.N.T. and Radiotherapy departments. His proptosis improved considerably (Fig. 6). Unfortunately, there was some blurring of vision in the right eye.
FIG. 6 Marked improvement of the right proptosis after excision of the tumour. There is still some external widening of the nose. Notice the fine scar of the lateral rhinotomy: 'The Handsome Incision'.
The problem of mild crusting in the large antro-nasal cavity was dealt with by simple local medication. There has been no evidence of any residual or recurrent lesion in this patient's nasal cavity, nor any distant metastases for eighteen months after the primary excision. Pathology In 1873, Rouget, while studying tissues of some vertebrates, found amoeboid cells with unusual contractile power in the spaces around the blood capillaries and called them 'cellules adventices'. In 1922, Vimtrup and Krogh confirmed this observation by the discovery of similar cells in other life forms and named them 'Rouget cells'. One year later, a Swiss histologist called Zimmermann (1923) described in detail a special type of cell which was wrapped around the capillaries of some vertebrates. It had variable forms, some of which morphologically resembled muscle cells, and he gave the name 'pericyte' to it, believing that it was a modified muscle cell.
482
R. GUDRUN
In 1942, Stout and Murray were studying glomus tumours and they found that the epithelioid cells of Masson in the glomus tumour were the same cells as those which were called pericytes by Zimmermann. They also observed that the cells were able to contract in spite of the absence of myofibrils in them and, in vitro, they discarded their epithelioid shape and became amoeboid, like the cells described by Rouget almost seventy years previously. Nowadays, pericytes are histologically well-established cells. They are round or spindle-shaped, with long branching processes, and applied to the outer walls of the venous capillaries and post-capillary venules. They are believed to arise from the primitive mesenchymal cells (Rhodin, 1968). Then, they take the form of primitive smooth muscle cells which eventually undergo transformation into mature smooth muscle cells. The ultrastructure of these pericytes shows them to be completely surrounded by basement membrane except for the occasional small areas of contact either with other pericytes or with endothelial cells (Hahn et al, 1973). Their cytoplasmic contents are: a few large mitochondria, abundant free ribosomes, prominent Golgi complexes and fine filaments which occur singly or in small bundles widely scattered throughout the cytoplasm. The function of the pericytes is uncertain. They are believed to provide mechanical support for the capillaries and to regulate the size of their lumen. They also synthesize their own basement membrane and nearby collagen fibres (Rhodin, 1968). Excessive proliferation of these pericytes in any part of the body will lead to the formation of a haemangiopericytoma. This is a rare vascular tumour which does not have any specific gross features to enable one to recognize it clinically. It behaves like other angiomatous tumours by the tendency to begin before birth or early in life, to grow locally either as a nodule with limited infiltration or with more persistent and aggressive invasion and rarely with metastases (Stout and Murray, 1942). Wherever there are capillaries, haemangiopericytoma may be expected to arise but it has a predilection for the subcutaneous and muscular tissues. It forms a firm painless and slowly growing mass, often nodular and well-localized. It does not show any discoloration to indicate its vascular origin, because the capillaries are emptied of their blood by compression of massive numbers of pericytes surrounding them. It is partially or completely encapsulated but this capsule usually contains tumour formations. It may undergo calcification but actual necrosis of the tumour tissue is apparently rare (Stout, 1949). Basically the tumour consists of a large number of capillaries, each one being lined by flat endothelial cells with intact connective tissue sheath. The pericytes are found outside the sheath and in the spaces between the capillaries. Each pericyte is characteristically enclosed by reticular fibres. As
HAEMANGIOPERICYTOMA IN OTOLARYNGOLOGY
483
for the tumour cells, the majority have a well-defined nucleus which is either rounded or elongated, with a prominent nuclear membrane; the nucleus is also finely stippled, with granular chromatin, and contains small nucleoli (Kauffman and Stout, 1960). Histological examination is the only way to diagnose this tumour. Haematoxylin and Eosin stain can be used to identify the tumour, but Laidlaw's silver reticulin stain is essential to confirm it. This stain makes the sheath of the capillaries black and easily recognizable; it also demonstrates that the tumour cells are actually outside the sheath. This significant point helps to differentiate it from another vascular tumour called 'haemangioendothelioma', with the tumour cells inside the capillary sheath (Stout and Murray, 1942). It is possible sometimes to see a mixed lesion of haemangiopericytoma and haemangioendothelioma, especially in children and very young adults, Congenital haemangiopericytomas are less cellular and show a greater proportion of inter-cellular collagen and reticulin fibres. One should be very certain that the growth is basically vascular and not a tumour whose cells are nourrshed by a rich vascular network such as one sees in many tumours of endocrine organs, in some Ewing tumours of bone marrow, and elsewhere (Stout and Murray, 1942). Degree of malignancy This is very difficult to assess; the clinical course which the tumour will follow cannot be foretold from its histological appearance (O'Brien and Brasfield, 1965). Some show aggressive growth without known metastases (Stout, 1949). Most of the malignant haemangiopericytomas are found in elderly people. They metastasize by lymphatics and blood stream to the lungs, bones, liver, and local lymph nodes. There are no distinct criteria to differentiate between benign and malignant haemangiopericytoma. The number of mitoses is very variable but still significant. Permanent foci of mitoses and particularly a number of evenly distributed mitoses should be looked upon with great suspicion. Tumour cells are approximately of the same size but the tendency to grow close to each other in a cohesive fashion is lost. Reticulin fibres no longer separate the cells into regular-sized groups. There is an apparent decrease in the number of the vessels (Kauffman and Stout, 1960). Differential diagnosis The diagnosis of a haemangiopericytoma depends entirely on its histological features, and the following tumours may be confused with it: glomus tumour, haemangioendothelioma, vascular leiomyoma, undifferentiated or metastatic carcinoma, Kaposi's sarcoma, Ewing's sarcoma, leiomyoblastoma, vascular meningioma, sclerosing
484
R. GUDRUN
haemangioma, treated malignant melanoma, neurilemmoma, vascular portions of fibrosarcoma, paraganglioma, and some of the endocrine tumours. Clinical features
Being such a rare tumour, haemangiopericytoma represents only slightly more than 1 per cent of all vascular neoplasma (Walike and Bailey, 1971). It can occur at any age. The congenital type has been reported in neonates. Cassel reported a patient of 92 years old with a haemangiopericytoma of the omentum (Stout and Cassel, 1943). In a large series of 307 cases reviewed by Kauffman and Stout in 1960, only 10 • 1 per cent were in the paediatric age group. On the contrary the tumour has some predilection for the 5th and 6th decades. Sex distribution is more or less equal. Aetiology The cause of the tumour formation is uncertain but several interesting observations have been made in the past which are worth mentioning in order to cast some light on this mysterious tumour. 1. Trauma Stout's series of haemangiopericytomas in 1949 included a male patient, 21 years old, who was hit by a nail in the right infra-orbital region; a few days later a tumour appeared which, when excised three years later, was found to be 1 cm. beneath the epidermis, encapsulated, soft, pink in colour and mottled with haemorrhages. A history of trauma is found more frequently in children than in adults. Kauffman and Stout (1960) mentioned that out of 31 children with haemangiopericytoma, 6 gave a history of an area of ecchymosis or a swelling that failed to recede, as the first sign of the tumour. Whether or not the damage to the capillaries stimulates proliferation of the pericytes leading to tumour formation, is not certain enough to attach a firm aetiological significance to it. 2. Steroid therapy Masson (1950), while experimenting on rats with desoxycorticosterone, noticed that, in addition to hypertension, multiple vascular lesions appeared in the kidneys and other viscera. These lesions showed proliferation of perivascular cells, probably the pericytes. The first case of laryngeal haemangiopericytoma, reported by Walike and Bailey in 1971, also demonstrates the concept of prolonged steroid therapy as a possible underlying factor in the causation of this tumour.
HAEMANGIOPERICYTOMA IN OTOLARYNGOLOGY
485
The patient was a female, 64 years old, who was treated with variable doses of prednisone (25-100 mg. daily) for a period of twenty months in order to keep her gross pemphigus vulgaris under control. In the middle of this treatment she developed multiple non-ulcerated nodules on the lower lip, tongue and soft palate. These were locally excised and their histology showed haemangiopericytoma. One month before she died (due to poor physical status), she became hoarse, and examination revealed a nodular bosselated vascular tumour encasing the epiglottis completely. A biopsy confirmed the same lesion. Collagen as a connective tissue provides mechanical support for the capillaries, and steroids are known physiologically to inhibit collagen formation; a poorly sulphonated ground substance accummulates in the connective tissues. Pericytes presumably are able to synthesize nearby collagen fibres to support the capillaries as part of their function. When the capillaries are deprived of this mechanical support, it is possible that they may break down, and, in order to supply more collagen in response to the increased demand, pericytes may have to undergo hyperplasia. This is only a suggestion; obviously the matter needs further study. Site Haemangiopericytoma may arise in any part of the body but it prefers subcutaneous and muscular tissues. One third of the lesions are found in the head and neck and the rest in the following areas: trunk, limbs, retroperitoneal space, mesentery, orbit, tongue, nasal cavity, pericardium, meninges, maxilla, pleural cavity, ileum and larynx. The size is as variable as the site. Table I shows that the largest nasal haemangiopericytoma was 2 1 - 5 x l - 7 x l - 3 cm., extending from the nostrils to the level of the uvula, and the smallest was 2 x 2 cm. (Case No. 14). Symptoms These depend on the site and size of the tumour. The main symptom is a painless mass which is firm and well-localized and often nodular. Pain, if present, is due to pressure on the local nerve endings as the tumour itself does not contain any nerve fibres. Nasal haemangiopericytoma is mainly polypoid in shape, soft in texture, with grey or reddish colour. It grows slowly but is locally infiltrative and occasionally metastatic. It causes nasal obstruction, partial or complete, unilateral or bilateral. Epistaxis is another common symptom, which is usually mild and recurrent, but it can be massive in children. From its gross appearance, it is not possible to predict whether or not a nasal haemangiopericytoma is malignant.
1949 Stout
1959 Woodson
1961 Murashima
1964 Rhodes et al.
1964 Rhodes et al
1
2
3
4
5
Author
Year
C
57
53
4
—
66
Age
Massive epistaxis
Epistaxis
Symptoms
F
Epistaxis
M Nasal obstruction
F
F
Sex
TABLE I
13 years
3 years
—
—
Duration Orbit
Spread
Follow-up
Pre-operative ligation No recurrence for three years of external carotid artery. Excised by snare. Followed by radiotherapy: 3000 r.
Excised 4 times in Died one month 7 years, last after the last operation: operation exenteration of orbit
Treatment
Nasal septum
Excised by nasal snare via post-nasal space
No recurrence for 3 years
Nasal septum Pre-operative ligation No follow-up notes eroded of external carotid artery, excised via lateral rhinotomy. 10 radon seeds implanted into nasal septum
Left spheno- Nasopharynx ethmoid recess
Died three weeks Right nasal Nasal septum Pre-operative later due to tracheotomy. eroded, cavity general cachexia antrum and Incomplete excision nasopharynx via lateral rhinotomy. involved Radium needles inserted: five 2 m g \ giving two 1 mgj 4200 r.
Left middle Nasopharynx meatus
Ethmoid sinus
Site
REVIEW OF NASAL HAEMANGIOPERICYTOMAS (1949-1978)
a
62
35
1968 Gill and Mehra
1968 Lenczyk
1970 Eneroth et al. 50
7
8
9
51
1964 Rhodes et al.
6
Nasal obstruction and epistaxis
M Epistaxis
M Recurrent epistaxis
F
M Nasal obstruction
None
No recurrence for two years
Local excision 3 times No recurrence for in 17 years. Removed two years via craniotomylateral rhinotomy approach. Cavity skin-grafted
Two excisions in 3 years. Excised via external ethmoidectomy
Cribriform First diagnosis: Cataract. Neck plate and anaplastic carcinoma; lymph nodes left lateral excised via Denker's 12 years later. wall of nose operation with block Re-excised. eroded dissection (no Second diagnosis: palpable nodes). haemangioRadiotherapy: 3000 r. pericytoma
Roof of Erosion of right nasal cribriform cavity plate
Left ethmoid region
Right Nasal septum Bleeding benign tumour Post-operative cribriform eroded removed 8 years cerebro-spinal plate previously. Excised fluid leak. No via lateral rhinotomy recurrence for 16 months
One month Left ethmoid region
20 years
6 years
12 years
TABLE I—continued
OO
4^
8 § 8
g
(-1
S
g
q
2
o
a
X «
F
M Nasal obstruction and epistaxis
M Epistaxis
26
12
24
1972 Alii and Singh
1973 Hahn et al.
1973 Benveniste and Harris
13
14
Nasal obstruction
Nasal obstruction
12
F
1970 Eneroth et al. 29
11
Nasal obstruction
1970 Eneroth^o/. 80
10
Right posterior ethmoid
Left ethmoid
Right ethmoid
—
8 years
Ten months Left ethmoid
Six months
None
None
None
Nasopharynx
Right nasal None cavity
TABLE \—continued
No follow-up notes
No recurrence for 5 years
No recurrence for 18 months
Polypoid tumour No recurrence for removed with partial 2J years ethmoidectomy one year previously. Diagnosis: capillary haemangioma. Re-excised with cryo-probe (20 minutes at -195° C)
Excised with snare. Recurred 6 months later, re-excised
Local excision. Temporary tape on carotid artery
Excised via Denker's operation with ethmoidectomy
Bleeding polyp removed No recurrence for two years previously, five years diagnosis: spindlecell sarcoma. Local excision again followed by radiotherapy: 2700 r.
B
UJ
JO /-*
oo 00
HAEMANGIOPERICYTOMA IN OTOLARYNGOLOGY
489
Associated conditions
It is interesting to mention the following two conditions in order to illustrate some of the hidden aspects of this tumour. Hypoglycaemia: Howard and Davis in 1959 reported a case of retroperitoneal haemangiopericytoma in a 17-year-old female patient who had relief of hypoglycaemic attacks and musculinization after excision of the tumour. It has been suggested that unusually large tumours have the ability to use glucose rather excessively. Paullada et al. (1968) reported a similar case in support of this observation. Hypertension: Robertson et al. (1967) reported an interesting case of hypertension in a 16-year-old female patient, caused by a renin-secreting haemangiopericytoma. Radiological appearances
Haemangiopericytoma, whether in the nasal cavity or any other part of the body, gives a soft- tissue shadow on the X-ray. Pressure erosion of the surrounding bones may occur (Kent, 1957). Calcification in the tumour mass appears as spicules (Kent, 1957), or a whorl-like pattern indicating to some extent its vascular origin (Mujahed et al., 1959). Distant metastases of a malignant haemangiopericytoma cannot be distinguished radiologically from other sarcomatous secondaries. Intracranial haemangiopericytoma needs special investigations: brain scan, air encephalogram, angiogram, etc., for accurate assessment of the site, size and vascularity of the lesion. Treatment Surgery
From all the data available as a result of this survey, it is possible to conclude that the treatment of choice for this tumour is wide surgical excision. 'Shelling out' of the lesion is inadequate and contraindicated (Walike and Bailey, 1971). Rhodes et al. (1964) suggest limited excision in nasal haemangiopericytoma, but compatible with a cure, in order to avoid gross deformity of the nose. This practice will certainly increase the incidence of recurrences, especially as the tumour has an unusual tendency to local recurrence after primary excision, and also to the late appearance of metastases. Therefore, a nasal lesion should be treated in the same manner as haemangiopericytoma in other parts of the body (Eneroth et al., 1970). The interval between surgical excision and the appearance of metastases is extremely variable. McCormack and Gallivan (1954) reported an interval of 13 years. Schirger et al. (1958) reported a case of extradural haemangiopericytoma
490
R. GUDRUN
of the thoracic spinal canal which recurred locally 26 years after excision. Because of this very late appearance of metastases, a life-long follow-up is mandatory (Walike and Bailey, 1971). It is rewarding to remind ourselves to perform a biopsy of this lesion with caution because of its marked vascularity and tendency to massive bleeding. It may be noticed in Table I that in Cases No. 2 and 4, the external carotid artery was ligated pre-operatively and, in Case No. 12, a temporary tape was applied to the carotid artery during the actual resection of the tumour. Cryosurgery has also been used in the excision of recurrent nasal haemangiopericytoma, as seen in the Case No. 14, in order to minimize the blood loss to a remarkable degree. Radiotherapy It seems very difficult to assess precisely the value of radiotherapy in the management of haemangiopericytoma, for the simple reason that only a very small number of the cases are treated by this method and the clinical data available are not sufficient to give it a proper evaluation. Nevertheless, one can always learn from the experience of others in this respect. Kent (1957) irradiated a soft-tissue haemangiopericytoma of the leg with 4,400 r in 22 days. The mass did not decrease in size but became soft. Stout (1949) subjected an 11-year-old child with a mass lateral to the rectum, to a dose of 7,300 r and through three fields over a period of eight months. The tumour shrank but did not disappear. It remained quiscent for several years and then recurred. Mujahed and his colleagues (1959) gave a tumour dose of 4,930 r in 24 days post-operatively to a tumour in the arm, yet it recurred a year later. These failures do not mean that radiotherapy is to be deemed useless in the management of this tumour, because it is still a valuable adjunt, to be considered in the following conditions (Friedman and Egan, 1960): i. When the tumour is too extensive to resect. ii. For the treatment of inoperable distant metastases. iii. For the treatment of post-operative residual lesions, whether known or expected, iv. For the treatment of lesions in the limbs when amputation is not desirable. Since the behaviour of any particular haemangiopericytoma is unpredictable from the microscopic picture and in view of the high rate of local recurrence, it would seem desirable to irradiate the operative site of all resected lesions (Mujahed et ah, 1959). The lethal dose, according to Friedman and Egan (1960), probably
HAEMANGIOPERICYTOMA IN OTOLARYNGOLOGY
491
TABLE II REVIEW OF HAEMANGIOPERICYTOMAS IN OTOLARYNGOIJOGY ( 1 9 4 2 - 1 9 7 8 )
Year
Author
Age
Treatment
Site
Sex
1942 Stout and Murray
31
M Infra-auricular Excised. Follow-up was not allowed area
1949 Stout
13
M Base of tongue Excised twice in 14 months
1952 Wise
-
-
Maxilla
Excision
1959 Small and Bloom
57
M Floor of the mouth
Enucleated. No follow-up
1960 Kauffman and Stout
10
M Pre-auricular
Excised. No recurrence for 9 months
1960 Kauffman and Stout
New-born
1960 Kauffman and Stout
6
M Tongue
Excision. No recurrence for 6 months
1960 . Kauffman and Stout
13
M Tongue
Excision. Recurred after 14 months
1963 Powell and Suehs
45
F
Maxilla
Partial maxillectomy and post-operative radiotherapy: 6500 r. Lung metastases one year later. Died after two years
-
-
Maxilla
Maxillectomy. No recurrence for six years
1965 Das and Gans
60
F
Buccal cavity
Excision. No follow-up
1968 Sage and Salman
16
M Mandible
Excision. Lung metastases 4 years later, died
1968 Rewell
56
M Maxillary alveolus
Excision. No recurrence for 16 months
1970 Chhangani and Saxena
26
M Post-auricular Excision. No follow-up
1971 Walike and Bailey
64
F
Larynx
Radiotherapy. Died before it was completed
1972 Shukla et al.
42
F
Maxilla
Radiotherapy up to 2400 r: no response, so excised. No recurrence for 8 months
1974 Taguchi et al.
47
M Larynx
1976 Caldarelli and Sperling
66
F
1978 Ferlito
50
M Larynx
1965 O'Brien and Brasfield
F
Pinna
Maxilla
Excision. No recurrence for 8 years
Excision. Post-operative radiotherapy: 6120 r. Radical maxillectomy. No recurrence for two years Patient died before any active treatment was given
492
R. GUDRUN
lies in the range of 7,500 r to 9,000 r in 30 to 60 days in most parts of the body. This high dose entails a certain risk of radiation injury and can be administered only with super-voltage X-rays or gamma teletherapy. Backwinkel and Diddams (1970), analysed 177 cases of haemangiopericytoma treated by surgery alone, with a cure rate of 53-1 per cent, compared to 15 cases treated by radiotherapy alone, with a cure rate of 13-3 per cent up to five years follow-up. This means that there is no conclusive evidence that radiotherapy is effective enough to be employed for the primary treatment of this tumour. Yet, it may reduce and even eliminate the high incidence of local recurrences and it may also reduce the incidence of occasional distant metastases. As regards other methods of irradiation, it may be noticed in Table I that, in Case No. 4, 10 radon seeds were implanted in the nasopharynx of the patient after surgical excision of the tumour. Also, in Case No. 6, the excision was incomplete and radium needles were inserted into the lesion: five 2 mg. and two 1 mg. needles, delivering a dose of 4,200 r. Unfortunately, the follow-up data do not encourage one to make any conclusive remark about the effectiveness of these techniques of radiotherapy. Chemotherapy The role of chemotherapy in the treatment of malignant haemangiopericytoma is rather obscure. Most attempts in the past ended either with absolute failure or with doubtful benefits, until 1971, when Ortega and his colleagues reported a case in a 2|-year-old child with malignant haemangiopericytoma treated for the first time by chemotherapy for control of bone metastases. This child had a right retroperitoneal tumour involving the right kidney and inseparable from the inferior vena cava. There were no distant metastases at this stage and the excision was incomplete. He was put on the following drug therapy: Actinomycin D (15 micro gm./kg./day, intravenously for five consecutive days, every three months). Cyclophosphamide (oral 5 mg./kg./day). Vincristine (0 05 mg./kg., intravenously, once weekly). In two weeks the tumour regressed 10 per cent. Then, radiotherapy was added to this treatment with a dose of 4,035 r in four weeks. Within 4 months, the lesion regressed another 25 per cent. Skeletal survey at this time showed bone metastases in the 7th thoracic vertebra, left scapula and left ischium. Methotrexate (1-25 mg./kg., intravenously per week) was substituted for vincristine. Cyclophosphamide was discontinued after one month due to haemorrhagic cystitis. No change was made in the actinomycin D dose. After another four months with this treatment, it was possible to excise
HAEMANGIOPERICYTOMA IN OTOLARYNGOLOGY
493
the tumour completely with right nephrectomy. Histological examination of the peri-aortic lymph nodes and right kidney, and biopsies of ail the bone lesions, showed no viable tumour cells. The child remained completely asymptomatic for 2\ years. Chest X-ray and skeletal survey remained normal. So also did the development of the child. This unique case demonstrates that combination therapy can be utilized to treat large haemangiopericytomas, to induce considerable regression in order to facilitate the final complete and safe excision. Prognosis and results
Haemangiopericytoma is highly malignant, not in a 5-year concept but on a life-time basis (O'Brien and Brasfield, 1965). Local recurrences are very common. Distant metastases have been reported to occur in 11-7 per cent by Kauffman and Stout (1960); while Fisher (1960) reported 45 per cent and admitted that the mortality of the tumour had been underestimated. Death may occur between 5 and 21 years after diagnosis. The recurrence rate is variable according to the organs and systems involved. Tumours of the central nervous system show 80 per cent recurrence rate, while tumours of the musculo-skeletal systems show only 50 per cent (Backwinkel and Diddams, 1970). Only one case of metastasizing nasal haemangiopericytoma has been reported (by Eneroth et al, 1970) among the fourteen previous cases, and 12 years after surgical excision (i.e. 7 per cent). Seven out of fourteen cases (50 per cent) showed local recurrences for periods of 16 months to 7 years. No tumour known to have been congenital is known to have been malignant (Stout, 1949). Summary
Haemangiopericytoma is a rare vascular tumour with variable pathological behaviour. It arises from the proliferation of special cells called 'pericytes' which are found outside the blood capillaries. There is no specific predilection for any site in the body. Clinically and histologically, it can be benign or malignant, but this differentiation sometimes becomes rather a hard task for the pathologist. Wide surgical excision is the treatment of choice. Radiotherapy and chemotherapy can be valuable adjuncts. Only fourteen cases of nasal haemangiopericytoma have been reported in the literature and these are individually set out in Table I. Another case is reported in this paper, with a review of all the tumours in the field of Otorhinolaryngology since 1942. Acknowledgements
I would like to thank Mr. V. T. Hammond, Consultant E.N.T. Surgeon, St. Thomas' Hospital, for his help in preparing this paper and
494
R. GUDRUN
for his kind permission to publish the case report. My thanks are also due to Professor J. R. Tighe, Department of Surgical Pathology, for the photomicrographs. REFERENCES ALLI, A. F., and SINGH, S. P. (1972) Journal of Laryngology and Otology, 86, 405. BACKWINKEL, K. D., and DIDDAMS, J. A. (1970) Cancer, 25, 896.
BENVENISTE, R. J., and HARRIS, H. E. (1973) Archives of Otolaryngology, 98, 358. BERDJIS, C. C. (1957) Oncologia {Basel), 10, 336. CALDARELLI, D. D., and SPERLING, R. L. (1976) Archives of Otolaryngology, 102, 49. CHHANGANI, D. L., and SAXENA, R. K. (1970) Journal of Laryngology and Otology, 84, 457. DAS, A. K., and GANS, B. J. (1965) Journal of Oral Surgery, 23, 456. ENEROTH, C. M., FLUUR, E., SODERBERG, G., and ANGGARD, A. (1970) Laryngoscope, 80, 17.
FERLITO, A. (1978) Journal of Laryngology and Otology, 92, 511. FISHER, J. H. (1960) Journal of Canadian Medical Association, 83, 1136. FRIEDMAN, M., and EGAN, J. W. (1960) Radiology, 74, 721.
GILL, B. S., and MEHRA, Y. N. (1968) Journal of Laryngology and Otology, 82, 839. HAHN, M. J., DAWSON, R., ESTERLY, J. A., and JOSEPH, D. J. (1973) Cancer, 31, 255.
HOWARD, J. W., and DAVIS, P. L. (1959) Medical Journal of Delaware State, 31, 29. KAUTFMAN, S. L., and STOUT, A. P. (1960) Cancer, 13, 695.
KENT, K. H. (1957) American Journal of Roentgenology, 77, 347. LENCZYK, J. M. (1968) Archives of Otolaryngology, 87, 536. MCCORMACK, L. J., and GALLIVAN, W. E. (1954) Cancer, 7, 595.
MASSON, G. M. C. (1950) Archives of Pathology, 49, 641. MURASHIMA, J. (1961) Otolaryngology {Tokyo), 33, 537. MUJAHED, Z., VASILAS, A., and EVANS, J. A. (1959) American Journal of Roentgenology,
82, 658. O'BRIEN, P., and BRASFIELD, R. D. (1965) Cancer, 18, 249. ORTEGA, J. A., FINKLESTEIN, J. Z., and HITTLE, R. (1971) Cancer, 27, 730. PAULLADA, J. J., LISCI-GARMLLA, A., and GONZALES-ANGULO, A. (1968) American Journal
of Medicine, 44, 990. POWELL, D. B., and SUEHS, O. W. (1963) Texas Journal of Medicine, 59, 690. REWELL, R. E. (1968) Journal of Laryngology and Otology, 82, 261. RHODES, R. E., BROWN, H. A., and HARRISON, L. G. (1964) Archives of Otolaeyngology,
79, 505. RHODIN, J. A. G. (1968) Journal of Ultrastructure Research, 25, 452. ROBERTSON, P. W., KLEMIAN, A., HARDING, L. K., and WALTERS, G. (1967) American Journal
of Medicine, 43, 963. ROUGET, C. (1873) Quoted by BERDJIS, C. C. (1957). SAGE, H. H., and SALMAN, I. (1968) Journal of Oral Surgery, 3, 275. SCHIRGER, A., UIHLEIN, A., PARKER, H. L., and KERNCHAN, J. W. (1958) Proceedings of
Mayo Clinic, 33, 347. SHUKLA, G. K., DAYAL, D., and GUPTA, K. R. (1972) Journal of Laryngology and Otology,
86, 399. SMALL, I., and BLOOM, H. (1959) Journal of Oral Surgery, 12, 65. STOUT, A. P., and MURRAY, M. R. (1942) Annals of Surgery, 116, 26. STOUT, A. P., and CASSEL, C. (1943) Surgery, 13, 578.
STOUT, A. P. (1949) Cancer, 2, 1027. TAGUCHI, E. (1974) Otolaryngology (Tokyo), 46, 21. VIMTRUP, B., and KROGH, A. (1922) Quoted by BERDJIS, C. C. (1957).
WALIKE, J. W., and BAILEY, B. J. (1971) Archives of Otolaryngology, 93, 345. WISE, R. A. (1952) Archives of Surgery, 65, 201. WOODSON, W. B. (1959) Laryngoscope, 69, 445. ZIMMERMANN, K. W. (1923) Quoted by BERDJIS, C. C. (1957).
Haemangiopericytoma in otolaryngology By ROGER GUDRUN
Introduction HAEMANGIOPERICYTOMA is a rare vascular tumour. Since 1942, it has fascinated pathologists as well as clinicians by its unpredictable and variable biological behaviour. Kauffman and Stout (1960) called it an exasperating tumour. In 1942, Stout and Murray used the term 'haemangiopericytoma' for the first time and, after prolonged tissue culture studies, recognized it as a pathological entity. They presented nine patients with this tumour one of whom could be considered as the first case ever reported in Otolaryngology. He was a male adult patient of 31 with a pedunculated lesion of the infra-auricular region. In 1949, Stout published his second series which included 25 cases of haemangiopericytoma: Case No. 4 with an oropharyngeal lesion (base of the tongue), and Case No. 11 with the first nasal haemangiopericytoma. Walike and Bailey (1971) reported the first case of haemangiopericytoma of the larynx in a female patient, 64 years old, with gross chronic pemphigus vulgaris who developed stridor secondary to a nodular bosselated lesion of the epiglottis. The tumour arises from proliferation of special cells called 'Pericytes' which are found outside the capillaries. Hence, it can arise anywhere in the body. Diagnosis of the tumour is not possible clinically and sometimes even histologically. Consequently, there is always some indecisiveness regarding the management of these tumours. In the present paper a case of nasal haemangiopericytoma is reported, to be added to the previous fourteen cases in the literature. The evolution and ultrastructure of the tumour is described in addition to an outline of the modes of treatment which may be adopted when confronted with this unusual vascular tumour. Case report A.K., a 61-year-old white male, was referred by his family doctor to the E.N.T. department of St. Thomas' Hospital, London, on 15 December 1976, with six months' history of right-sided nasal obstruction. He had one spell of epistaxis three weeks prior to his visit. He also noticed slow painless bulging of the right eye. His past medical history, apart from appendicectomy in 1946, did not reveal any significant information. 477
478
R. GUDRUN
FIG. 1 Large soft-tissue mass occupying the right nasal cavity. Right antrum seems opaque.
FIG. 2 Tomogram of the paranasal sinuses. No definite bone erosion of the orbit or anterior cranial fosa.
HAEMANGIOPERICYTOMA IN OTOLARYNGOLOGY
479
Clinically, he had right proptosis without any visual defect. There was obvious external widening of the nose. The right nasal cavity was filled almost completely with a greyish polypoid mass pushing the nasal septum to the left. The post-nasal space showed the same mass protruding from the posterior choana. The rest of his upper food and air passages did not reveal any gross abnormality. There were no palpable lymph nodes in the neck. X-ray of the para-nasal sinuses showed an opaque right antrum with possible erosion of its medial wall (Fig. 1). Tomograms did not indicate any bone destruction in relation to the orbit and anterior cranial fossa (Fig. 2). No abnormality was found in the blood or chest X-ray. On 31 December 1976, the patient was admitted to hospital for examination under general anaesthesia and biopsy. The latter caused a blood loss of 800 ml., due to the vascularity of the tumour. Histological diagnosis was: malignant haemangiopericytoma (Figs. 3, 4 and 5). On 21 January 1977, through a right lateral rhinotomy incision, the tumour was found to arise from the right ethmoid region. It had eroded the medial wall of the orbit in places but the orbital periosteum was intact. It extended superiorly into the right frontal sinus but, on removal, the sinus wall appeared norrnal. The left sinus contained some pus but no tumour. There was a defect in the anterior cranial fossa and the dura seemed to be involved. Oedematous antral mucosa was stripped off. The sinus itself appeared free of the lesion. The naso-antral cavity was packed with BIPP, and the wound closed in two layers. Blood loss throughout the excision was one unit which was replaced. The mass removed measured roughly 5 x 4 x 3 cm. in size, and the histological
FIG. 3 Large number of round and spindle-shaped cells are seen to surround the vascular lumina. (H. & E., X400).
480
R. GUDRUN
FIG. 4 Multiple vascular spaces with sharply demarcated reticulin sheaths. (Laidlaw's Silver stain x 100).
FIG. 5 Silver impregnation showing the perivascular arrangement of the pericytes. (Laidlaw's stain x400).
;
HAEMANGIOPERICYTOMA IN OTOLARYNGOLOGY
481
sections confirmed the pre-operative diagnosis of malignant haemangiopericytoma. Therefore, it was decided to follow the surgical excision by a course of radiotherapy. On 7 February 1977, Cobalt 60 teletherapy, planned with two wedges aiming at 5,500 r in 12 treatments over 28 days to the right side of the face, was commenced. The patient, after completion of his treatment, was assessed regularly by both E.N.T. and Radiotherapy departments. His proptosis improved considerably (Fig. 6). Unfortunately, there was some blurring of vision in the right eye.
FIG. 6 Marked improvement of the right proptosis after excision of the tumour. There is still some external widening of the nose. Notice the fine scar of the lateral rhinotomy: 'The Handsome Incision'.
The problem of mild crusting in the large antro-nasal cavity was dealt with by simple local medication. There has been no evidence of any residual or recurrent lesion in this patient's nasal cavity, nor any distant metastases for eighteen months after the primary excision. Pathology In 1873, Rouget, while studying tissues of some vertebrates, found amoeboid cells with unusual contractile power in the spaces around the blood capillaries and called them 'cellules adventices'. In 1922, Vimtrup and Krogh confirmed this observation by the discovery of similar cells in other life forms and named them 'Rouget cells'. One year later, a Swiss histologist called Zimmermann (1923) described in detail a special type of cell which was wrapped around the capillaries of some vertebrates. It had variable forms, some of which morphologically resembled muscle cells, and he gave the name 'pericyte' to it, believing that it was a modified muscle cell.
482
R. GUDRUN
In 1942, Stout and Murray were studying glomus tumours and they found that the epithelioid cells of Masson in the glomus tumour were the same cells as those which were called pericytes by Zimmermann. They also observed that the cells were able to contract in spite of the absence of myofibrils in them and, in vitro, they discarded their epithelioid shape and became amoeboid, like the cells described by Rouget almost seventy years previously. Nowadays, pericytes are histologically well-established cells. They are round or spindle-shaped, with long branching processes, and applied to the outer walls of the venous capillaries and post-capillary venules. They are believed to arise from the primitive mesenchymal cells (Rhodin, 1968). Then, they take the form of primitive smooth muscle cells which eventually undergo transformation into mature smooth muscle cells. The ultrastructure of these pericytes shows them to be completely surrounded by basement membrane except for the occasional small areas of contact either with other pericytes or with endothelial cells (Hahn et al, 1973). Their cytoplasmic contents are: a few large mitochondria, abundant free ribosomes, prominent Golgi complexes and fine filaments which occur singly or in small bundles widely scattered throughout the cytoplasm. The function of the pericytes is uncertain. They are believed to provide mechanical support for the capillaries and to regulate the size of their lumen. They also synthesize their own basement membrane and nearby collagen fibres (Rhodin, 1968). Excessive proliferation of these pericytes in any part of the body will lead to the formation of a haemangiopericytoma. This is a rare vascular tumour which does not have any specific gross features to enable one to recognize it clinically. It behaves like other angiomatous tumours by the tendency to begin before birth or early in life, to grow locally either as a nodule with limited infiltration or with more persistent and aggressive invasion and rarely with metastases (Stout and Murray, 1942). Wherever there are capillaries, haemangiopericytoma may be expected to arise but it has a predilection for the subcutaneous and muscular tissues. It forms a firm painless and slowly growing mass, often nodular and well-localized. It does not show any discoloration to indicate its vascular origin, because the capillaries are emptied of their blood by compression of massive numbers of pericytes surrounding them. It is partially or completely encapsulated but this capsule usually contains tumour formations. It may undergo calcification but actual necrosis of the tumour tissue is apparently rare (Stout, 1949). Basically the tumour consists of a large number of capillaries, each one being lined by flat endothelial cells with intact connective tissue sheath. The pericytes are found outside the sheath and in the spaces between the capillaries. Each pericyte is characteristically enclosed by reticular fibres. As
HAEMANGIOPERICYTOMA IN OTOLARYNGOLOGY
483
for the tumour cells, the majority have a well-defined nucleus which is either rounded or elongated, with a prominent nuclear membrane; the nucleus is also finely stippled, with granular chromatin, and contains small nucleoli (Kauffman and Stout, 1960). Histological examination is the only way to diagnose this tumour. Haematoxylin and Eosin stain can be used to identify the tumour, but Laidlaw's silver reticulin stain is essential to confirm it. This stain makes the sheath of the capillaries black and easily recognizable; it also demonstrates that the tumour cells are actually outside the sheath. This significant point helps to differentiate it from another vascular tumour called 'haemangioendothelioma', with the tumour cells inside the capillary sheath (Stout and Murray, 1942). It is possible sometimes to see a mixed lesion of haemangiopericytoma and haemangioendothelioma, especially in children and very young adults, Congenital haemangiopericytomas are less cellular and show a greater proportion of inter-cellular collagen and reticulin fibres. One should be very certain that the growth is basically vascular and not a tumour whose cells are nourrshed by a rich vascular network such as one sees in many tumours of endocrine organs, in some Ewing tumours of bone marrow, and elsewhere (Stout and Murray, 1942). Degree of malignancy This is very difficult to assess; the clinical course which the tumour will follow cannot be foretold from its histological appearance (O'Brien and Brasfield, 1965). Some show aggressive growth without known metastases (Stout, 1949). Most of the malignant haemangiopericytomas are found in elderly people. They metastasize by lymphatics and blood stream to the lungs, bones, liver, and local lymph nodes. There are no distinct criteria to differentiate between benign and malignant haemangiopericytoma. The number of mitoses is very variable but still significant. Permanent foci of mitoses and particularly a number of evenly distributed mitoses should be looked upon with great suspicion. Tumour cells are approximately of the same size but the tendency to grow close to each other in a cohesive fashion is lost. Reticulin fibres no longer separate the cells into regular-sized groups. There is an apparent decrease in the number of the vessels (Kauffman and Stout, 1960). Differential diagnosis The diagnosis of a haemangiopericytoma depends entirely on its histological features, and the following tumours may be confused with it: glomus tumour, haemangioendothelioma, vascular leiomyoma, undifferentiated or metastatic carcinoma, Kaposi's sarcoma, Ewing's sarcoma, leiomyoblastoma, vascular meningioma, sclerosing
484
R. GUDRUN
haemangioma, treated malignant melanoma, neurilemmoma, vascular portions of fibrosarcoma, paraganglioma, and some of the endocrine tumours. Clinical features
Being such a rare tumour, haemangiopericytoma represents only slightly more than 1 per cent of all vascular neoplasma (Walike and Bailey, 1971). It can occur at any age. The congenital type has been reported in neonates. Cassel reported a patient of 92 years old with a haemangiopericytoma of the omentum (Stout and Cassel, 1943). In a large series of 307 cases reviewed by Kauffman and Stout in 1960, only 10 • 1 per cent were in the paediatric age group. On the contrary the tumour has some predilection for the 5th and 6th decades. Sex distribution is more or less equal. Aetiology The cause of the tumour formation is uncertain but several interesting observations have been made in the past which are worth mentioning in order to cast some light on this mysterious tumour. 1. Trauma Stout's series of haemangiopericytomas in 1949 included a male patient, 21 years old, who was hit by a nail in the right infra-orbital region; a few days later a tumour appeared which, when excised three years later, was found to be 1 cm. beneath the epidermis, encapsulated, soft, pink in colour and mottled with haemorrhages. A history of trauma is found more frequently in children than in adults. Kauffman and Stout (1960) mentioned that out of 31 children with haemangiopericytoma, 6 gave a history of an area of ecchymosis or a swelling that failed to recede, as the first sign of the tumour. Whether or not the damage to the capillaries stimulates proliferation of the pericytes leading to tumour formation, is not certain enough to attach a firm aetiological significance to it. 2. Steroid therapy Masson (1950), while experimenting on rats with desoxycorticosterone, noticed that, in addition to hypertension, multiple vascular lesions appeared in the kidneys and other viscera. These lesions showed proliferation of perivascular cells, probably the pericytes. The first case of laryngeal haemangiopericytoma, reported by Walike and Bailey in 1971, also demonstrates the concept of prolonged steroid therapy as a possible underlying factor in the causation of this tumour.
HAEMANGIOPERICYTOMA IN OTOLARYNGOLOGY
485
The patient was a female, 64 years old, who was treated with variable doses of prednisone (25-100 mg. daily) for a period of twenty months in order to keep her gross pemphigus vulgaris under control. In the middle of this treatment she developed multiple non-ulcerated nodules on the lower lip, tongue and soft palate. These were locally excised and their histology showed haemangiopericytoma. One month before she died (due to poor physical status), she became hoarse, and examination revealed a nodular bosselated vascular tumour encasing the epiglottis completely. A biopsy confirmed the same lesion. Collagen as a connective tissue provides mechanical support for the capillaries, and steroids are known physiologically to inhibit collagen formation; a poorly sulphonated ground substance accummulates in the connective tissues. Pericytes presumably are able to synthesize nearby collagen fibres to support the capillaries as part of their function. When the capillaries are deprived of this mechanical support, it is possible that they may break down, and, in order to supply more collagen in response to the increased demand, pericytes may have to undergo hyperplasia. This is only a suggestion; obviously the matter needs further study. Site Haemangiopericytoma may arise in any part of the body but it prefers subcutaneous and muscular tissues. One third of the lesions are found in the head and neck and the rest in the following areas: trunk, limbs, retroperitoneal space, mesentery, orbit, tongue, nasal cavity, pericardium, meninges, maxilla, pleural cavity, ileum and larynx. The size is as variable as the site. Table I shows that the largest nasal haemangiopericytoma was 2 1 - 5 x l - 7 x l - 3 cm., extending from the nostrils to the level of the uvula, and the smallest was 2 x 2 cm. (Case No. 14). Symptoms These depend on the site and size of the tumour. The main symptom is a painless mass which is firm and well-localized and often nodular. Pain, if present, is due to pressure on the local nerve endings as the tumour itself does not contain any nerve fibres. Nasal haemangiopericytoma is mainly polypoid in shape, soft in texture, with grey or reddish colour. It grows slowly but is locally infiltrative and occasionally metastatic. It causes nasal obstruction, partial or complete, unilateral or bilateral. Epistaxis is another common symptom, which is usually mild and recurrent, but it can be massive in children. From its gross appearance, it is not possible to predict whether or not a nasal haemangiopericytoma is malignant.
1949 Stout
1959 Woodson
1961 Murashima
1964 Rhodes et al.
1964 Rhodes et al
1
2
3
4
5
Author
Year
C
57
53
4
—
66
Age
Massive epistaxis
Epistaxis
Symptoms
F
Epistaxis
M Nasal obstruction
F
F
Sex
TABLE I
13 years
3 years
—
—
Duration Orbit
Spread
Follow-up
Pre-operative ligation No recurrence for three years of external carotid artery. Excised by snare. Followed by radiotherapy: 3000 r.
Excised 4 times in Died one month 7 years, last after the last operation: operation exenteration of orbit
Treatment
Nasal septum
Excised by nasal snare via post-nasal space
No recurrence for 3 years
Nasal septum Pre-operative ligation No follow-up notes eroded of external carotid artery, excised via lateral rhinotomy. 10 radon seeds implanted into nasal septum
Left spheno- Nasopharynx ethmoid recess
Died three weeks Right nasal Nasal septum Pre-operative later due to tracheotomy. eroded, cavity general cachexia antrum and Incomplete excision nasopharynx via lateral rhinotomy. involved Radium needles inserted: five 2 m g \ giving two 1 mgj 4200 r.
Left middle Nasopharynx meatus
Ethmoid sinus
Site
REVIEW OF NASAL HAEMANGIOPERICYTOMAS (1949-1978)
a
62
35
1968 Gill and Mehra
1968 Lenczyk
1970 Eneroth et al. 50
7
8
9
51
1964 Rhodes et al.
6
Nasal obstruction and epistaxis
M Epistaxis
M Recurrent epistaxis
F
M Nasal obstruction
None
No recurrence for two years
Local excision 3 times No recurrence for in 17 years. Removed two years via craniotomylateral rhinotomy approach. Cavity skin-grafted
Two excisions in 3 years. Excised via external ethmoidectomy
Cribriform First diagnosis: Cataract. Neck plate and anaplastic carcinoma; lymph nodes left lateral excised via Denker's 12 years later. wall of nose operation with block Re-excised. eroded dissection (no Second diagnosis: palpable nodes). haemangioRadiotherapy: 3000 r. pericytoma
Roof of Erosion of right nasal cribriform cavity plate
Left ethmoid region
Right Nasal septum Bleeding benign tumour Post-operative cribriform eroded removed 8 years cerebro-spinal plate previously. Excised fluid leak. No via lateral rhinotomy recurrence for 16 months
One month Left ethmoid region
20 years
6 years
12 years
TABLE I—continued
OO
4^
8 § 8
g
(-1
S
g
q
2
o
a
X «
F
M Nasal obstruction and epistaxis
M Epistaxis
26
12
24
1972 Alii and Singh
1973 Hahn et al.
1973 Benveniste and Harris
13
14
Nasal obstruction
Nasal obstruction
12
F
1970 Eneroth et al. 29
11
Nasal obstruction
1970 Eneroth^o/. 80
10
Right posterior ethmoid
Left ethmoid
Right ethmoid
—
8 years
Ten months Left ethmoid
Six months
None
None
None
Nasopharynx
Right nasal None cavity
TABLE \—continued
No follow-up notes
No recurrence for 5 years
No recurrence for 18 months
Polypoid tumour No recurrence for removed with partial 2J years ethmoidectomy one year previously. Diagnosis: capillary haemangioma. Re-excised with cryo-probe (20 minutes at -195° C)
Excised with snare. Recurred 6 months later, re-excised
Local excision. Temporary tape on carotid artery
Excised via Denker's operation with ethmoidectomy
Bleeding polyp removed No recurrence for two years previously, five years diagnosis: spindlecell sarcoma. Local excision again followed by radiotherapy: 2700 r.
B
UJ
JO /-*
oo 00
HAEMANGIOPERICYTOMA IN OTOLARYNGOLOGY
489
Associated conditions
It is interesting to mention the following two conditions in order to illustrate some of the hidden aspects of this tumour. Hypoglycaemia: Howard and Davis in 1959 reported a case of retroperitoneal haemangiopericytoma in a 17-year-old female patient who had relief of hypoglycaemic attacks and musculinization after excision of the tumour. It has been suggested that unusually large tumours have the ability to use glucose rather excessively. Paullada et al. (1968) reported a similar case in support of this observation. Hypertension: Robertson et al. (1967) reported an interesting case of hypertension in a 16-year-old female patient, caused by a renin-secreting haemangiopericytoma. Radiological appearances
Haemangiopericytoma, whether in the nasal cavity or any other part of the body, gives a soft- tissue shadow on the X-ray. Pressure erosion of the surrounding bones may occur (Kent, 1957). Calcification in the tumour mass appears as spicules (Kent, 1957), or a whorl-like pattern indicating to some extent its vascular origin (Mujahed et al., 1959). Distant metastases of a malignant haemangiopericytoma cannot be distinguished radiologically from other sarcomatous secondaries. Intracranial haemangiopericytoma needs special investigations: brain scan, air encephalogram, angiogram, etc., for accurate assessment of the site, size and vascularity of the lesion. Treatment Surgery
From all the data available as a result of this survey, it is possible to conclude that the treatment of choice for this tumour is wide surgical excision. 'Shelling out' of the lesion is inadequate and contraindicated (Walike and Bailey, 1971). Rhodes et al. (1964) suggest limited excision in nasal haemangiopericytoma, but compatible with a cure, in order to avoid gross deformity of the nose. This practice will certainly increase the incidence of recurrences, especially as the tumour has an unusual tendency to local recurrence after primary excision, and also to the late appearance of metastases. Therefore, a nasal lesion should be treated in the same manner as haemangiopericytoma in other parts of the body (Eneroth et al., 1970). The interval between surgical excision and the appearance of metastases is extremely variable. McCormack and Gallivan (1954) reported an interval of 13 years. Schirger et al. (1958) reported a case of extradural haemangiopericytoma
490
R. GUDRUN
of the thoracic spinal canal which recurred locally 26 years after excision. Because of this very late appearance of metastases, a life-long follow-up is mandatory (Walike and Bailey, 1971). It is rewarding to remind ourselves to perform a biopsy of this lesion with caution because of its marked vascularity and tendency to massive bleeding. It may be noticed in Table I that in Cases No. 2 and 4, the external carotid artery was ligated pre-operatively and, in Case No. 12, a temporary tape was applied to the carotid artery during the actual resection of the tumour. Cryosurgery has also been used in the excision of recurrent nasal haemangiopericytoma, as seen in the Case No. 14, in order to minimize the blood loss to a remarkable degree. Radiotherapy It seems very difficult to assess precisely the value of radiotherapy in the management of haemangiopericytoma, for the simple reason that only a very small number of the cases are treated by this method and the clinical data available are not sufficient to give it a proper evaluation. Nevertheless, one can always learn from the experience of others in this respect. Kent (1957) irradiated a soft-tissue haemangiopericytoma of the leg with 4,400 r in 22 days. The mass did not decrease in size but became soft. Stout (1949) subjected an 11-year-old child with a mass lateral to the rectum, to a dose of 7,300 r and through three fields over a period of eight months. The tumour shrank but did not disappear. It remained quiscent for several years and then recurred. Mujahed and his colleagues (1959) gave a tumour dose of 4,930 r in 24 days post-operatively to a tumour in the arm, yet it recurred a year later. These failures do not mean that radiotherapy is to be deemed useless in the management of this tumour, because it is still a valuable adjunt, to be considered in the following conditions (Friedman and Egan, 1960): i. When the tumour is too extensive to resect. ii. For the treatment of inoperable distant metastases. iii. For the treatment of post-operative residual lesions, whether known or expected, iv. For the treatment of lesions in the limbs when amputation is not desirable. Since the behaviour of any particular haemangiopericytoma is unpredictable from the microscopic picture and in view of the high rate of local recurrence, it would seem desirable to irradiate the operative site of all resected lesions (Mujahed et ah, 1959). The lethal dose, according to Friedman and Egan (1960), probably
HAEMANGIOPERICYTOMA IN OTOLARYNGOLOGY
491
TABLE II REVIEW OF HAEMANGIOPERICYTOMAS IN OTOLARYNGOIJOGY ( 1 9 4 2 - 1 9 7 8 )
Year
Author
Age
Treatment
Site
Sex
1942 Stout and Murray
31
M Infra-auricular Excised. Follow-up was not allowed area
1949 Stout
13
M Base of tongue Excised twice in 14 months
1952 Wise
-
-
Maxilla
Excision
1959 Small and Bloom
57
M Floor of the mouth
Enucleated. No follow-up
1960 Kauffman and Stout
10
M Pre-auricular
Excised. No recurrence for 9 months
1960 Kauffman and Stout
New-born
1960 Kauffman and Stout
6
M Tongue
Excision. No recurrence for 6 months
1960 . Kauffman and Stout
13
M Tongue
Excision. Recurred after 14 months
1963 Powell and Suehs
45
F
Maxilla
Partial maxillectomy and post-operative radiotherapy: 6500 r. Lung metastases one year later. Died after two years
-
-
Maxilla
Maxillectomy. No recurrence for six years
1965 Das and Gans
60
F
Buccal cavity
Excision. No follow-up
1968 Sage and Salman
16
M Mandible
Excision. Lung metastases 4 years later, died
1968 Rewell
56
M Maxillary alveolus
Excision. No recurrence for 16 months
1970 Chhangani and Saxena
26
M Post-auricular Excision. No follow-up
1971 Walike and Bailey
64
F
Larynx
Radiotherapy. Died before it was completed
1972 Shukla et al.
42
F
Maxilla
Radiotherapy up to 2400 r: no response, so excised. No recurrence for 8 months
1974 Taguchi et al.
47
M Larynx
1976 Caldarelli and Sperling
66
F
1978 Ferlito
50
M Larynx
1965 O'Brien and Brasfield
F
Pinna
Maxilla
Excision. No recurrence for 8 years
Excision. Post-operative radiotherapy: 6120 r. Radical maxillectomy. No recurrence for two years Patient died before any active treatment was given
492
R. GUDRUN
lies in the range of 7,500 r to 9,000 r in 30 to 60 days in most parts of the body. This high dose entails a certain risk of radiation injury and can be administered only with super-voltage X-rays or gamma teletherapy. Backwinkel and Diddams (1970), analysed 177 cases of haemangiopericytoma treated by surgery alone, with a cure rate of 53-1 per cent, compared to 15 cases treated by radiotherapy alone, with a cure rate of 13-3 per cent up to five years follow-up. This means that there is no conclusive evidence that radiotherapy is effective enough to be employed for the primary treatment of this tumour. Yet, it may reduce and even eliminate the high incidence of local recurrences and it may also reduce the incidence of occasional distant metastases. As regards other methods of irradiation, it may be noticed in Table I that, in Case No. 4, 10 radon seeds were implanted in the nasopharynx of the patient after surgical excision of the tumour. Also, in Case No. 6, the excision was incomplete and radium needles were inserted into the lesion: five 2 mg. and two 1 mg. needles, delivering a dose of 4,200 r. Unfortunately, the follow-up data do not encourage one to make any conclusive remark about the effectiveness of these techniques of radiotherapy. Chemotherapy The role of chemotherapy in the treatment of malignant haemangiopericytoma is rather obscure. Most attempts in the past ended either with absolute failure or with doubtful benefits, until 1971, when Ortega and his colleagues reported a case in a 2|-year-old child with malignant haemangiopericytoma treated for the first time by chemotherapy for control of bone metastases. This child had a right retroperitoneal tumour involving the right kidney and inseparable from the inferior vena cava. There were no distant metastases at this stage and the excision was incomplete. He was put on the following drug therapy: Actinomycin D (15 micro gm./kg./day, intravenously for five consecutive days, every three months). Cyclophosphamide (oral 5 mg./kg./day). Vincristine (0 05 mg./kg., intravenously, once weekly). In two weeks the tumour regressed 10 per cent. Then, radiotherapy was added to this treatment with a dose of 4,035 r in four weeks. Within 4 months, the lesion regressed another 25 per cent. Skeletal survey at this time showed bone metastases in the 7th thoracic vertebra, left scapula and left ischium. Methotrexate (1-25 mg./kg., intravenously per week) was substituted for vincristine. Cyclophosphamide was discontinued after one month due to haemorrhagic cystitis. No change was made in the actinomycin D dose. After another four months with this treatment, it was possible to excise
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the tumour completely with right nephrectomy. Histological examination of the peri-aortic lymph nodes and right kidney, and biopsies of ail the bone lesions, showed no viable tumour cells. The child remained completely asymptomatic for 2\ years. Chest X-ray and skeletal survey remained normal. So also did the development of the child. This unique case demonstrates that combination therapy can be utilized to treat large haemangiopericytomas, to induce considerable regression in order to facilitate the final complete and safe excision. Prognosis and results
Haemangiopericytoma is highly malignant, not in a 5-year concept but on a life-time basis (O'Brien and Brasfield, 1965). Local recurrences are very common. Distant metastases have been reported to occur in 11-7 per cent by Kauffman and Stout (1960); while Fisher (1960) reported 45 per cent and admitted that the mortality of the tumour had been underestimated. Death may occur between 5 and 21 years after diagnosis. The recurrence rate is variable according to the organs and systems involved. Tumours of the central nervous system show 80 per cent recurrence rate, while tumours of the musculo-skeletal systems show only 50 per cent (Backwinkel and Diddams, 1970). Only one case of metastasizing nasal haemangiopericytoma has been reported (by Eneroth et al, 1970) among the fourteen previous cases, and 12 years after surgical excision (i.e. 7 per cent). Seven out of fourteen cases (50 per cent) showed local recurrences for periods of 16 months to 7 years. No tumour known to have been congenital is known to have been malignant (Stout, 1949). Summary
Haemangiopericytoma is a rare vascular tumour with variable pathological behaviour. It arises from the proliferation of special cells called 'pericytes' which are found outside the blood capillaries. There is no specific predilection for any site in the body. Clinically and histologically, it can be benign or malignant, but this differentiation sometimes becomes rather a hard task for the pathologist. Wide surgical excision is the treatment of choice. Radiotherapy and chemotherapy can be valuable adjuncts. Only fourteen cases of nasal haemangiopericytoma have been reported in the literature and these are individually set out in Table I. Another case is reported in this paper, with a review of all the tumours in the field of Otorhinolaryngology since 1942. Acknowledgements
I would like to thank Mr. V. T. Hammond, Consultant E.N.T. Surgeon, St. Thomas' Hospital, for his help in preparing this paper and
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