Lymphoreticular tumors of the orbit

Lymphoreticular tumors of the orbit

inr. 1. R,,dtmon Oncolo~.v Biol. Ph.& Vol. Pnnted in the U.S.A. All nghts reserved IO. pp 333-340 Copyght c 0360-3016~84 $3 00 t 00 1984 Pergamon...

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inr. 1. R,,dtmon Oncolo~.v Biol. Ph.& Vol. Pnnted in the U.S.A. All nghts reserved

IO.

pp

333-340 Copyght

c

0360-3016~84 $3 00 t 00 1984 Pergamon Press L:d

??Original Contribution LYMPHORETICULAR PETER

TUMORS

OF THE ORBIT

J. FITZPATRICK, M.B., F.R.C.P.(C), F.R.C.R.? The Princess Margaret Hospital, Toronto,

AND

SHARON MACKO,

M.D.:

Ontario

Lymphoreticular tumors in tbe orbit are uncommon. Only 42 patients were identified from over 2000 patients with tumors of lymphoid tisue seen between 1958 and 1979. The patients were divided into 3 groups: primary malignant, secondary malignant, and benign lymphoma. In the primary malignant lymphoma groups, there were 24 patients with a median age of 64 (40 to 87) years and a 2.4:1 female to male ratio: 2 cases were bilateral. In I9 (79%) patients with the lymphoma limited to one orbit the tumor was controlled in every case with dosesfrom 25 to 45 Gy. There were no serious complications. Subsequently lymphoma developed at other sites in 7 (37%) patients. The 5 and 10 year cause specific actuarial survival rates were 70 and 62%. In the 8 patients with secondary malignant lymphoma, the orbital disease was controlled by irradiation, although all patients required further treatment and died of their disease. Radiotherapy controlled all 7 patients with benign lymphoma without any complictitions. Orbit, Lympboreticular tumors, Radiotherapy.

INTRODUCTION Lymphoreticular tumors in the orbit are rare. There is difficulty both clinically and pathologically in establishing the diagnosis. Around the eye, lymphoid tissue is found in the subconjunctiva and lacrimal gland, which accounts for most lymphoreticuloses developing at these sites. They arise as a result of hyperplasia or the malignant transformation of indigenous lymphoid tissue. We have not seen a case of intraocular lymphoma. A few leukemic patients will develop tumor infiltrates in the uveal tract, but these patients are not part of this study. Histologically, the tumors are benign or malignant. The benign lymphoma, commonly called a pseudolymphoma or pseudotumor, is a reactive lymphoid hyperplasia. The malignant lymphomas can be subdivided into primary or secondary tumors, depending on whether the first sign of disease was in the orbit of a later manifestation of systemic disease. The orbit is broadly defined as the cavity containing the tissues and organs contributing to the function of the eye including its coverings. Topographically the tumors were classified as to their origin from the conjunctiva and eyelid or from the lacrimal gland and retrobulbar tissues. The purpose of this study was an attempt to elucidate the clinical course of malignant lymphoma and other lymphoid lesions involving the orbit.

METHODS AND MATERIALS Between 1958 and 1979, 42 patients with lymphoreticular tumors in the orbit were seen in the eye clinic at the Princess Margaret Hospital. Three patients seen briefly but not treated or followed by us were excluded from the study. This retrospective analysis of patients treated in a 21 year period was handicapped by the quality of some of the records. Some factors such as minor ocular changes that we now seek prospectively in every patient were not recorded. All patients were seen by an ophthalmologist and a radiation oncologist. Every primary lymphoma and pseudolymphoma was confirmed histologically but it was felt unnecessary to biopsy the orbital tumor in those patients with known widespread lymphoma. A full lymphoma work-up, which changed during the study period, was performed on patients with primary lymphoma but not pseudolymphoma. The patients were reviewed and are reported in three groups; primary malignant lymphoma, secondary malignant lymphoma and benign lymphoma.

tRadiation Oncologist and Associate Professor of Radiology, University of Toronto. $.Resident, Radiotherapy Department. Reprint requests to: Dr. P. Fitzpatrick, Princess Margaret Hospital, 500 Shelbourne Street, Toronto, Ontario, Canada M4X 1K9.

Acknowledgemenrs-This report represents the combined efforts of many people, in particular, Dr. G. A. Thompson, Dr. M. Easterbrook, and Dr. B. Gallie. Miss Evelyn Eisenreich performed the secretarial tasks. Accepted for publication 26 October 1983.

Primary malignant lymphoma In this group the first symptom

or sign of disease was related to the eye or orbit. There were 24 patients with a female : male ratio of 2.4 : I (17 women and 7 men) with a median age of 65 (40-87 years). Following the lym-

333

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Radiation Oncology ??Biology ??Physics

phoma work-up, 5 patients were found to have disease outside of one orbit. In 2 patients, both orbits were involved with one having widespread lymphoma. Two others had ipsilateral cervical nodes and another generalized disease (Table 1). Lymphoma was limited to one orbit in 19 patients. Symptoms, usually present for about 6 months, of which swelling around the eye was the most common, are listed in Table 2. The conjunctiva was the only focus of disease in 11 patients and the only site of orbital lymphoma in 15. However, altogether it was involved in 21 patients. The tumors were classified using the Rappaport histological classification; this revealed a preponderance of diffuse lymphocytic tumors (Table 3). There were no cases of Hodgkin’s disease. Treatment and results. Irradiation of the orbit was our first planned treatment for 19 patients with limited disease; it was successful in every patient (Table 4). Four patients had been treated by surgery prior to referral, but all recurred within a few weeks. Subsequent irradiation caused a rapid and complete disappearance of the lymphoma in three patients. The fourth, with a diffuse, well differentiated lymphocytic lymphoma, declined radiotherapy, had three further operations and died 4 years after diagnosis with extensive disease in both orbits. Althogether, the periocular tissues of 23 patients were irradiated. The only failure resulted from a geographic miss with lymphoma recurring in the anterior orbit after the posterior orbit was irradiated in continuity with the nasopharynx and regional nodes. Fifteen patients were treated with an anterior direct 250 kV field and the other 8 with Yo radiation using a direct anterior field in 3, lateral fields in 2 and a wedge pair in 3. Doses ranged from 25 Gy in 10 treatments in 2 weeks to 45 Gy in 15 treatments in 3 weeks. In most cases, the lymphoma had completely disappeared within one month of completing irradiation (Figs. lA, B, C). The side effects were insignificant and complications recorded in only 3 patients. One developed entropion of the lower lid, another mild epiphera and the third a 1. The conjunctiva was the only focus of disease in 11 patients and the only orbital site of lymphoma in IS, however, the conjunctiva was involved in 21 patients Table

PRIMARYMALIGNANTLYMPHOMAORBIT

24 PATIENTS

22 "NILATEL

1

I\ 19 CONFINEDTO 7 CERVICALNODES ORBIT 1 GENERALIZED 11 CONJUNCTIVA 5 CONJUNCTIVA+ ORBIT 1 LACRIMALGLAND + ORBIT 1 LACRIMALSAC + ORBIT 1 SKIN EYELID

2 BILATERAL (1 GENERALIZED)

March 1984, Volume IO, Number 3

Table 2. The presenting symptoms for 22 patients with primary malignant tymphoma of the orbit SIGNS/SYIIPTOfiS SWELLING

20

VISUAL CHANGE

4

EPIPHORA

4

PROPTOSIS

4

PTOSIS

2

DISCORFORT

2

Table 3. Histology. There is a preponderance of lymphocytic tumors. The diffuse tumors show varying differentiation PRINARY MALIGNANT LYRPHOMA OF ORB11 (RAPPAPORT) NODULAR HlSTlOCYTlC

1

NODULAR MIXED

1

DIFFUSE LYMPHOCTYIC - WELL DIFF.

5

DIFFUSE LYNPHOCYTIC - INTERNEDlATEDIFF. 3 DIFFUSE LYMPHOCYTlC - POORLY DIFF.

3

DIFFUSE HISTIOCYTIC

2

DIFFUSE - UNDIFFERENTIATED

3

UNCLASSIFIED

6 24

TOTAL

Table 4. Radiotherapy controlled the orbital lymphoma in all 19 patients. Subsequently seven patients developed lymphoma elsewhere 19 PATIENTS (1 BlLATERAL) LYNPHOM CONFlNEDTO ORBIT i RADIOTHERAPY

19 LOCAL CONTROL

-'i\ 17 NO RECURRENCE 5 - 17 YRS

7 1 3 1 1

RECURRENCES OPPOSITEORBIT CERVICALNODES SKIN GENERALIZED

DCWD 1, DLPD 1. DH 2. DU 1. UNCLASS.2'

*Histology: DLWD = diffuse lymphocytic well differentiated; DLPD = diffuse lymphocytic poorly differentiated; DH = diffuse histocytic; DU = diffuse undifferentiated; UNCLASS = unclassified.

cornea1 ulcer. This last patient persisted in rubbing the eye with a dirty hand and in all probability this should not be listed as a complication of treatment. Undoubtedly some other changes secondary to radiotherapy such as a slightly dry eye or minor cataract occurred but were not recorded. They would have been insignificant to the patients but currently we assess all

Lymphoreticular

tumors of the orbit ??P. J. FITZPATRICKAND S. MACKO

335

(C)

(4

Fig. 1. A, B, C. This retrobulbar diffuse, poorly differentiated lymphocytic lymphoma caused 4 mm proptosis. Treated with a “Co wedge pair technique to 3500 cGy and with protection of the anterior segment, this tumor remains controlled at 4 years. There have been no complications. B. CT scanuhowing retrobulbar lymphoma. C. Four years following radiotherapy the orbital lymphoma is controlled. for any changes that develop following radiotherapy. To date, with periods ranging from 4 to 12 years, orbital irradiation has rendered 12 of the 19 patients with disease limited to this site free of lymphoma. Lymphoma has recurred in seven patients. In two the first site of recurrence was in the opposite orbit, in three the cervical lymph nodes, in one the skin of the cheek and in the other at multiple sites. The histology of those patients who recurred is shown in Table 4. The patient with conjunctival lymphoma and ipsilateral cervical nodes recurred in the nasopharynx and contralateral cervical nodes after 16 months. After treatment with radiation, he is alive and disease free 19 years later. The one patient with lymphoma cutis was first treated by biopsy excision. Five months later the lymphoma recurred in the eyelid and cervical nodes. Following irradiation she remains well 7 years later. Of the 2 patients with generalized lymphoma, treated by radiotherapy and

patients

Radiation Oncology ??Biology ??Physics

336

chemotherapy, one has died while the other is alive and disease free at 10 years. Among the 15 patients with orbital lymphoma limited to the conjunctiva, one was found to have generalized lymphoma and this subsequently developed in a second patient. Four of the 8 patients with lymphoma involving tissues other than the conjunctiva have developed generalized disease. In all, 4 patients have died from uncontrolled lymphoma including 3 in whom the diseaase initially appeared confined to the orbit. Four deaths have resulted from intercurrent disease. The 5 and 10 year cause specific actuarial survival rates are 70 and 62x, and the relapse-free rates 41% (Fig. 2). Secondary malignant lymphoma

These patients developed orbital lymphoma as part of a systemic disease in lymphatic tissues sometime after the initial treatment for lymphoma. There were 8 patients in this group, 4 males and 4 females, with a median age of 47 (37-79) years. One patient had bilateral lesions. Four patients had a nodular lymphocytic lymphoma, 3 a diffuse lymphocytic lymphoma and the other was a diffuse histiocytic lymphoma. The conjunctiva was involved in 7 patients and the retro-orbital tissues in 1. All patients had extensive disease. These patients were referred to the eye clinic, but undoubtedly more patients with generalized lymphoma develop orbital lesions. Treatment and results. Palliative irradiation was directed to the orbits to shrink the tumor and relieve symptoms. In every case a complete and rapid response, without complication, was obtained with doses of 20 Gy in five daily treatments or 30 Gy in 10 treatments given in 2 weeks (Figs. 3A and 3B). Each patient needed further treatment but the orbital tumor was controlled until death for periods from 9 months to 5 years. Benign lymphoma

There were 7 patients in this reactive lymphoid hyperplasia group. Five were female and 2 male with a median I

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Years Fig. 2. The five and 10 year cause specific actuarial survival rates were 70 and 62%. and the relapse-free rates 41%.

March 1984, Volume 10, Number 3

age of 52 (31-69) years. The median duration of symptoms was 8 months. Four patients developed periorbital swelling, 2 a red eye, 1 proptosis and 1 had diplopia. The conjunctiva was involved in 4 cases, the lacrimal gland in 1 and the retrobulbar tissues in 2. Four patients had been previously treated; an excision was attempted in 3, one on two occasions, and another had received steroids and one combination chemotherapy. Treatment and results. The involved orbit was irradiated in all 7 patients. For the 6 patients with anterior disease, a direct anterior 250 kV or @Co beam was used and 20 or 25 Gy given in 10 treatments in 2 weeks. One patient with proptosis from retrobulbar disease was irradiated to 35 Gy with a wedge pair @‘Co technique given in 15 treatments in 3 weeks. Each tumor had completely resolved with 2 months. There have been no recurrences (Figs. 4A & 4B). No radiotherapy complications are recorded. One patient with a conjunctival lesion had palpable cervical nodes when diagnosed. They started to enlarge 2 years later and were irradiated without histological confirmation following which they regressed rapidly. The patient is well and without evidence of disease 6 years later. Radiotherapy

Treatment is best considered from the extent of the disease rather than the histological diagnosis. Basically there are two plans according to whether the disease is limited to the conjunctiva and eyelids or involves the lacrimal gland or retro-orbital tissues. Tumors of the conjunctiva and eyelids are easily treated with a single anterior 250 kV 1.1 mm cu HVL field at 50 cm SSD. This modality is preferred for most patients because it is easier to shield the underlying eye. A 6 x 6 cm field will usually suffice and we recommend a dose of 25 Gy in 10 fractions in 2 weeks. Lacrimal and retrobulbar tumors tend to be more extensive and so the whole orbit must be treated. We use a @Co wedge pair technique with 7 x 7 cm fields to irradiate the entire orbital contents. A dose of 35 Gy in 15 treatments in 3 weeks has proved effective. All lymphoreticuloses of the orbit are radiosensitive. The response to treatment is rapid and in our experience complete. No lesion has been detected after 3 months. In nearly every case it is possible to reduce the dose to the radiosensitive and radiovulnerable anterior segment with appropriate shielding. For 250 kV radiation a 2 mm lead shield inserted into the beam or conjunctival sac will limit the dose to vital structures to 3%. In using a supervoltage wedge pair technique, the lateral field is angled backwards to miss the opposite eye and lead or tungsten shields are placed in both beams to minimize the dose to the anterior segment. DISCUSSION In non-Hodgkin’s lymphoma extranodal presentations are common with the incidence varying from 21

Lymphoreticular

tumors of the orbit ??P. J. FITZPATRICK AND S. MACKO

337

Fig. 3A. This patient with generalized histocytic lymphoma developed a mass in the left orbit. It produced 4mm of proptosis and interfered with his vision.

Fig. 3B. Treated with 3000cGy in 10 treatments the disease regressed and remained controlled until the patient’x death 8 months later.

to 64%.2.6.7 At the Princess Margaret

2 of these patients’ disease also involved the lacrimal gland or sac. The tumors can be difficult to diagnose both clinically and pathologically. A biopsy is essential but with the exception of small lesions an attempt at total resection is unnecessary. In all 4 of our patients in whom this was attempted the tumor recurred quickly. Subsequently the tumors were permanently controlled in the 3 that were irradiated. Histologically it can be difficult to distinguish orbital lymphomas from other conditions and sometimes there is a discrepancy between the diagnosis and clinical course. Morgan reviewed 26 patients with histologically “benign” and “malignant” lymphomas.‘O Of the 18 “benign” lymphomas, two developed disseminated lymphoma after 5 years, whereas only 4 of the 8 “malignant” lymphomas became generalized. One of our patients with benign lymphoma had palpable cervical lymph nodes, which enlarged some 2 years later. They were irradiated, disappeared, and there has been no evidence of disease since. There are few studies of primary orbital lymphomas using the Rappaport classification. Three of the 6 patients reported by Kelly et ai.* had histiocytic lymphomas, and of the 25 patients seen at the University of Michigan,9 14 were lympho-

Hospital between 1967 and 1978, among 1394 patients with nonHodgkin’s lymphoma, 142 (10%) presented in the head and neck. The incidence of patients presenting with disease in the orbit is unknown but we could only identify 24 of approximately 2000 patients (0.01%) seen between 1958 and 1978. However, when considered in relation to other orbital neoplasms, malignant lymphoma is not rare. There are two main clinical presentations depending on whether the disease is limited to the conjunctiva and eyelids or involves the lacrimal gland or retrobulbar tissues. In the former, the characteristic appearance is that of smooth. shiny, salmon-pink swelling which may be limited to one part of the bulbar or palpebral conjunctiva, or circumscribe the limbus and infiltrate the whole conjunctiva. Retrobulbar lesions limit ocular movements and cause proptosis, diplopia, edema of the eyelids, chemosis, and pain. Rarely is there reduced visual acuity or is the visual field constricted. As a result of pressure a large retrobulbar mass may cause striae on the optic fundus or papilledema. In our experience the conjunctiva was the most common site and was involved in 21 patients. Eight patients had true orbital lymphoma;

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Radiation Oncology ??Biology 0 Physics

Fig. 4A.

March 1984, Volume IO, Number 3

The patient has extensive benign reactive lymphoid hyperplasia of the conjunctiva.

Fig. 4B. Treated with 2500 cGy from a direct anterior 250 kV beam, the lesion dispersed and has been controlled for 5 years, The anterior segment was protected and there have been no complications.

cytic, 8 histiocytic and 3 were unclassified. Thirteen of our 22 patients had lymphocytic tumors of varying differentiation, but the numbers are too small to make any valid conclusions. All patients need a full lymphoma work-up and

careful ophthalmic assessement which should include the opposite orbit and a CT scan of the head. The lymphoma work-up should include a lymphangiogram, liver and spleen scan, chest X-ray and mediastinal tomograms, bone marrow biopsy and hematological and

Lymphoreticular

tumors of the orbit 0 P. J. FITZPATRICK AND S. MACKO

biochemical studies. Among our 24 patients 5 were found to have disease outside of one orbit and subsequently lymphoma developed at other sites in another 7. Altogether I1 of the 24 (46%) patients needed further treatment. While only 2 patients with conjunctival lymphoma limited to one orbit developed generalized disease, one initially and one later, 4 of 8 patients with orbital disease did so. Three deaths from among the 19 patients with disease limited to one orbit and treated with radiation have resulted from generalized lymphoma. We could not correlate these with histology. Kim and Fayos found no statistical difference in survival and disease free survival between patients with lymphocytic and histiocytic lymphoma.’ In the series of Calle et al., however, 2 of 34 patients with lymphocytic lymphoma compared with 10 of 14 patients with reticulosarcoma died of generalized disease.’ For this reason they recommended that these latter patients get a higher dose of radiation to the orbit and be considered for chemotherapy. Radiation therapy has become the standard treatment for primary malignant lymphomas of the orbit. Both techniques and doses have varied but most reports stress the importance of shielding radiovulnerable structures. Franklin advocates treating orbital disease with a single exposure of 8 Gy using a single direct orthovoltage field.5 Although this technique controls the lymphoma. complications were reported among 14 of 26 patients. Others prefer fractionated radiation therapy and multiple fields.6.9 In the series of Foster et al., 5 of 33 patients recurred in the anterior orbit in areas that received less than 12 GY.~ All were successfully retreated. The majority of our patients received 25 Gy in 10 treatments in 2 weeks or 35 Gy in 15 treatments in 3 weeks and only one recurred as a result of a geographic miss. The advent of CT scanning has helped to delineate the extent of disease and to enable accurate, safe treatment planning. Conjunctival lymphomas have a better prognosis than other orbital lymphomas. Calle er al. have stated that “no conjunctival localizations really are malignant”.’ In their series of the nine tumors that recurred, seven involved the orbit and two the lacrimal sac. Kim and Fayos. however, could find no statistical difference in survival between patients with orbital and conjunctival lymphomas.’ In our series, 2 of 12 irradiated patients with conjunctival lymphomas compared with 4 of 8 patients with orbital lymphoma subsequently developed generalized disease. This suggests that orbital involvement may signify a guarded prognosis although the number of patients are too small for a definitive conclusion. The 5 and 10 year cause specific actuarial survival rates of 70.4 and 62”/, are similar to the 78% 5 year actuarial survival rate reported by Kim and Fayos.’ When the orbit becomes involved with lymphoma as part of a systemic disease, radiotherapy is the treatment of choice to relieve symptoms and control the tumor.

339

These patients are seriously ill. and a disfiguring lesion which may interfere with vision adds to their distress. A rapid and complete response to a short course of irradiation can be anticipated, and although other treatment will be required for generalized disease the orbital tumor will probably be permanently controlled. The terms benign lymphoma, reactive lymphoid hyperplasia, pseudolymphoma, pseudotumor and nonspecific granuloma of the orbit have been used to describe inflammatory lesions of the orbital tissues of unknown etiology. They simulate a malignant neoplasm, and in particular, malignant lymphoma. The condition is well known to ophthalmologists and neurosurgeons and after derangements of the pituitary-thyroid axis, are the most common cause of unilateral proptosis. The incidence is unknown and it is one of the most difficult diagnoses to make pathologically. The lesions are reactive and inflammatory, however, and not neoplastic. The histology is described as a polymorphic infiltrate composed of mature lymphocytes, plasma cells, histiocytes, mature lymphoplasmacytoid cells, fibrosis, follicles and capillary endothelial proliferation. Here, the recent development of phenotype markers that establish the clonality of cells will help to differentiate between a benign reactive process and malignant lymphoma. A malignant lymphoma is monomorphic and monoclonal whereas the pseudolymphoma is polymorphic and polyclonal. It has been postulated that pseudolymphoma arises as a response to a nonbacterial agent and is similar to polyarteritis or Wegener’s granuloma.’ Rarely. the condition is bilateral but it never becomes generalized. These lesions frequently regress with steroids and prednisone 5 mg t.i.d. is recommended for a therapeutic trial. If the tumor does not dissolve then radiotherapy is an effective and safe treatment. The principal characteristics of these benign tumors include proptosis, limitation of movement, diplopia, edema of the eyelid, chemosis and pain. The visual acuity, visual fields and optic fundus usually remain normal but an expanding uncontrolled tumor will produce papilledema and optic atrophy. In our small series of seven patients, radiotherapy has proven effective to date, although one patient developed ipsilateral cervical nodes and these were irradiated without biopsy. No patient has developed a generalized Iymphoma.

SUMMARY Lymphoreticular disorders of the orbit essentially have two presentations. The first involves the conjunctiva or eyelid and the second the lacrimal gland or retrobulbar tissues. The anterior presentation is treated with a direct field and orbital lesions with a @Co wedge pair technique. Doses of 25 cGy or 3500 cGy in IO or 15 fractions delivered in 2 or 3 weeks is effective treatment, The radiovulnerable anterior segment of the eye is protected from radiation and the complications are

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For 24 patients with primary malignant lymphoma the 5 and 10 year cause specific actuarial survival rates are 70 and 62%, and the relapse-free rate 41%. In 19 patients with lymphoma limited to the orbit, irradiation has rendered the site free of disease for periods

minimal.

March 1984, Volume 10. Number 3

ranging from 4 to 12 years. Subsequently in this group lymphoma has developed elsewhere in 7 patients. Radiotherapy has effectively controlled the orbital disease in 7 patients with benign lymphoma and eight with secondary malignant lymphoma.

REFERENCES I. Call& R., Zajdela, A., Haye, C., Schlienger, P.: Primary malignant lymphoid tumours of the orbit-The eye and it’s adnexa. Eye Ear Nose and Throat Month. 54: 141-149, 1975.

2. Chabner, B.S., Johnson, R.E., Young, R.C., Canellos, G.P., Hubbard, S.P., Johnson, S.K., DeVita, V.T., Jr.: Sequential non-surgical staging of non-Hodgkin’s lymphomas. Ann. Intern. Med. 85: 149-154, 1976. 3. Faulds, J.S., Wear, A.R.: Pseudotumour of the orbit and Wegener’s granuloma. Lancer 2: 955-957, 1960. 4. Foster, S.C., Wilson, C.S., Tretter, P.K.: Radiotherapy of primary lymphoma of the orbit. Am. J. Roentgenol. 111: 343-349, 197 1. 5. Franklin, C.I.V.: Primary lymphoreticular tumours in the orbit. Clin. Radiol. 26: 137-140, 1975. 6. Fuller, L.M., Banker, F.L., Butler, J.J., Gamble, J.F.,

Sullivan, M.P.: The natural history of non-Hodgkin’s Stage I and II. Br. J. Cancer 31 (Suppl. II):

lymphomas 270-285, 7. Johnson,

1975.

R.E., Chretien, P.B., O’Connor, G.T., DeVita, V.T., Jr., Thomas, L.B.: Radiotherapeutic implications of prospective staging in non-Hodgkin’s lymphoma. Radiology 110: 655-657, 1974. 8. Kelly, A.G., Rosa+uribe, A., Kraus, T.: Orbital lymphomas and pseudolymphomas: A clinicopathologic study of 11 cases. Am. J. C/in. Path. 68: 377-386, 1977. 9. Kim, Y.H. and Fayos, J.V.: Primary orbital lymphoma: A Radiotherapeutic experience. Int. J. Radiat. Oncol. Biol. Phys. 1: 1099-1105, 1976. 10. Morgan, G.: Lymphocytic tumours of the conjunctiva. J. C/in. Path. 24: 585-595,

1971.