Primary Adenocarcinoma of the Lacrimal Gland

Primary Adenocarcinoma of the Lacrimal Gland A Retrospective Study Rebecca S. Heaps, MD,l Neil R. Miller, MD,I Daniel M. Albert, MD,z W. Richard Green, MD,l Susan Vitale, MHS 1 Background: Primary adenocarcinoma of the lacrimal gland is rare and usually appears in the literature as case reports. The authors retrospectively studied cases of primary adenocarcinoma of the lacrimal gland to determine which of the currently used methods was most effective in treating this tumor. Methods: The authors requested cases of primary adenocarcinoma of the lacrimal gland from orbital surgeons and ocular pathologists worldwide. Of the cases referred, 13 examples of primary adenocarcinoma of the lacrimal gland could be confirmed and studied for clinical features, management, and outcome. Results: The authors have follow-up data on all 13 patients. Six patients died of cancer, three are alive with recurrence, and four are alive and disease-free. Conclusion: Based on the results of this study, the authors ascertain that primary adenocarcinoma of the lacrimal gland is not inevitably fatal and should be treated with exenteration and adjuvant radiotherapy as soon as a histologic diagnosis is established. Shorter duration of symptoms before treatment appears to decrease the chance of metastases and increase the chance of long-term survival. Ophthalmology 1993; 100: 1856-1860

Primary adenocarcinoma of the lacrimal gland is so rare and the number of treated patients is so small that optimum therapy for this tumor has not been determined. We have gathered clinical and histopathologic data on 13 patients with a diagnosis of primary adenocarcinoma of the lacrimal gland to review the pathology, treatment, and clinical course of the patients. Our goal was to obtain information on all cases of primary adenocarcinoma of the lacrimal gland in elucidating the nature of this tumor and to propose a protocol for diagnosing and treating primary adenocarcinoma of the lacrimal gland.

Originally received: March 18, 1993. Manuscript accepted: May 14, 1993. I The Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore. 2 University of Wisconsin-Madison, Madison. Reprint requests to Neil R. Miller, MD, Wilmer Eye Institute, Maumenee B-109, 600 North Wolfe St, Baltimore, MD 21287-9204.

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Materials and Methods Clinical questionnaires and requests for pathology specimens of primary adenocarcinoma of the lacrimal gland were sent to ocular pathologists and orbital surgeons at all hospitals with accredited ophthalmology residency programs in the United States. We also requested similar information from several orbital specialists in Great Britain, Italy, France, Canada, and Australia. Clinical information requested included a patient profile, symptoms and their duration, means of diagnosis and treatment, and follow-up including the nature of any recurrence. Clinical information and pathologic material from 17 patients were received. All pathologic specimens were independently reviewed by two of the authors (WRG and DMA), both of whom are board-certified pathologists. Clinical data were tabulated and compared for all patients. Because the sample size was so small, statistical analyses were not undertaken.

Heaps et al . Primary Adenocarcinoma of the Lacrimal Gland cases (Fig 1). The thirteenth case (case 5) was thought to be primary adenocarcinoma by one pathologist, although the other pathologist diagnosed it as an adenoid cystic carcinoma.

Patient Profile Nine of the 13 patients are male. Ten are white and three are African-American. The average age at diagnosis was 50 years (range, 31-78 years) (Table 1).

Symptoms The most common symptom at presentation was a palpable mass (11 cases) that had been present for a period ranging from 3 weeks to 8 years (Table 1). Proptosis was present in seven patients. Other symptoms included pain, visual loss, ptosis, tearing, and rhinitis. Duration ofsymptoms before diagnosis ranged from 3 weeks to 20 years.

Diagnosis All 13 lesions were diagnosed by permanent histologic section (Table 2). Seven lesions were obtained by incisional biopsy and six by excisional biopsy.

Treatment

Figure 1. Pathology of primary lacrimal gland adenocarcinoma from a 78-year-old man who underwent orbital exenteration. A, low-power view shows multiple nests of malignant epithelial cells with prominent nuclei and dark-staining cytoplasm (hematoxylin-eosin; original magnification, X2S0). B, another field from the same specimen shows a nest of cells with an acinar structure (arrowheads) (hematoxylin-eosin; original magnification, X160).

Results Of the 128 surgeons and pathologists from whom we requested information, 22 did not respond, 75 replied that they had no cases of primary adenocarcinoma, 9 said they thought they had cases but did not refer them, and 22 returned both clinical and pathologic information on a total of 17 cases. Four of the lesions that were diagnosed as primary adenocarcinoma by the referring pathologist were diagnosed as a different lesion by both of our pathologists: adenoid cystic carcinoma (2), metastatic carcinoma (I), and spindle cell tumor (1). Of the remaining 13 cases, both of our pathologists agreed on the diagnosis of primary adenocarcinoma of the lacrimal gland in 12

Nine patients were treated surgically, eight with exenteration and one with en bloc removal as described by Henderson and Neault' (Table 2). Four patients refused further surgery. The one patient treated with en bloc resection (case 9) had an orbital mass for 4 months before diagnosis and had lung and bone metastases at the time of presentation. He was the only patient who was treated surgically based on frozen-section pathology that was later confirmed by permanent section. He died of pulmonary failure as a complication of metastases 7 months later. Twelve of 13 patients received radiation therapy. Seven of these patients had undergone previous exenteration. Four patients had undergone only excisional biopsy and one patient had en bloc resection before radiotherapy. Only one patient (case 7) received surgical treatment but did not have radiation therapy. This patient is alive with spinal cord metastases 2 years later. Two patients received chemotherapy. Patient 8 received chemotherapy in conjunction with radiotherapy and exenteration. She had an orbital mass of 8 years' duration and metastases to the liver and lung. Despite therapy, she died 1 year later of pneumonia as a consequence of cancer. Patient 3 also received chemotherapy over 1'12 years. He had an orbital mass and proptosis for only 3 months before diagnosis and had exenteration 2 weeks later. The chemotherapy and radiotherapy were intended to prevent recurrence. He is alive and free of recurrence 14 years later.

Follow-up We were able to obtain follow-up data on all 13 patients (Table 2). Six have died of their malignancy, three are

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Table 1. Patient Profile and Symptoms Case No.

Sex/ Race

Orbit

Age at Diagnosis (yrs)

1 2 3 4 5 6 7

M/white M/white M/white M/white M/white M/white M/white

R R L L R R L

43 72 40 32 78 46 75

3 wks

1 mo 3 wks

3 wks

8 9

F/white M/white

R L

34 71

8 yrs 4mos

4mos

10 11

F/Asian M/white

L R

31 58

4mos 6 mos

20 yrs

6 mos

12 13

F/Asian F/Asian

L R

41 32

4mos 6 wks

1 mo 1 yr

8 mos 1 yr

R

=

right, L

=

Mass

3 mos 2 mos

Proptosis

Pain

Visual Loss

Diplopia

Other Symptoms

Metastases

Erythema 3 wks Ptosis 8 mos 3 mos 2 mos 5 mos

3 mos

3 mos

Tearing 5 mos Lid edema 3 wks

4 mos

4mos

Liver, lung 1 mo Lung, bone 1 mo

2 mos

4 mos Erythema 6 mos Rhinitis 8 mos Lid edema 2 mos

2 wks

left.

Table 2. Symptoms Duration and Outcome Date Last Assessed

Symptoms before Diagnosis

Symptoms before treatment

Treatment

Alive, recurrence-free 1 2 3

10/22/92 10/21/92 10/22/92

1 mo 8 mos 3 mos

1.75 mos 9.5 mos 4 mos

4

1/22/92

2 mos

3 mos

Exenteration and R T Exenteration and R T Exenteration, R T and chemotherapy Exenteration and R T

Symptoms to Endpoint"

Diagnosis to Endpoint·

Treatment to Endpoint·

199 mos 50mos 173 mos

198 mos 42 mos 170 mos

197 mos 41 mos 169 mos

18 mos

16 mos

15 mos

Alive with recurrence 7/31/91 10/12/92 10/15/92 Date deceased 1/29/72

5 mos 1 mos 1 mos

6 mos 1.5 mos 2 mos

RT Exenteration and R T Exenteration

13 mos 26 mos 31 mos

8 mos 25 mos 30 mos

7 mos 24mos 29 mos

96 mos

96 mos

109 mos

13 mos

13 mos

9

3/2/82

4mos

4mos

11 mos

7 mos

7 mos

10 11 12 13

6/28/91 1/1/81 4/1/79 6/12/90

4mos 240 mos 8 mos 12 mos

5 mos 241 mos 7 mos 13.5 mos

Exenteration, R T, and chemotherapy En bloc resection and RT RT RT RT Exenteration and R T

5 6 7 Deceased 8

RT

=

radiation therapy .

• Date last assessed if patient is still alive, or date of death if patient is deceased.

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44mos 256 mos 28 mos 48 mos

40 16 20 36

mos mos mos mos

39 15 19 35

mos mos mos mos

Heaps et al . Primary Adenocarcinoma of the Lacrimal Gland alive with recurrent tumor, and four are alive without recurrence. Of the latter four patients, the lengths of time without evidence of recurrence since treatment are 2 years (case 4), 31/2 years (case 2), 14 years (case 3), and 16 1/2 years (case 1). Of the six patients who died, the duration from presentation of symptoms to death ranged from 11 months to 22 years. Three of the six (cases 10,11, and 12) refused surgical intervention. Case 8 had an orbital mass for 8 years before exenteration was performed followed by radiation therapy and chemotherapy. She died 1 year later. Case 9 had symptoms for only 4 months before treatment. He had metastases at presentation and died 7 months after surgery. Case 13 had symptoms for 1 year before diagnosis. She underwent exenteration and radiation therapy after acute onset of visual loss from a hemorrhage into the tumor. She died 3 years later. Three patients currently are alive with evidence of recurrence. Case 5 refused definitive surgical treatment and he is alive 1 year later with residual tumor after an incisional biopsy. Case 6 had exenteration performed only 6 weeks after he noted orbital swelling. He recently has had evidence of regional lymph node involvement 2 years after surgery and will receive further surgical treatment. Case 7 was treated surgically with exenteration after only an 8-week duration oflid swelling and proptosis. Radiation therapy was planned but not performed. He is now receiving radiotherapy for metastases to the spine.

Discussion Primary adenocarcinoma of the lacrimal gland is rare. Most cases of this tumor appear in the literature as case reports; however, several authors have written about series of patients and have examined primary adenocarcinoma as an entity separate from other malignancies. In 1978, Font and Gamel 2 studied 256 cases of epithelial tumors of the lacrimal gland that included 19 cases of adenocarcinoma arising de novo. The duration of symptoms before treatment for these patients ranged from 1 week to 15 years (mean, 2.2 years). Ninety-three percent of the patients had recurrence of their tumor, and there was only a 34% 5-year survival. These authors did not discuss the specific treatment received by their patients with primary adenocarcinoma of the lacrimal gland, nor did they discuss the relationship of duration of symptoms or type of treatment to survival. Henderson 3 reported four patients with primary adenocarcinoma of the lacrimal gland in 1980. Three of the four patients died within 18 months of extensive surgery but the fourth patient was alive 19 years postoperatively, despite a recurrence in the pre-auricular lymph node that was treated with excision and radical neck dissection. Wright 4 had ten patients with adenocarcinoma in his study of lacrimal gland tumors in 1982. Since the study was published, several of these patients have been determined to have adenoid cystic carcinomas (personal correspondence with one of the authors [NRM]).

Brada and Henk 5 published a report in 1987 that included 12 patients with adenocarcinoma of the lacrimal gland. Unfortunately, as has been the case with most studies of lacrimal gland tumors, the primary adenocarcinomas were analyzed together with other tumors such as undifferentiated carcinomas and mixed malignant tumors. It is therefore impossible to determine from this study the effects of duration of symptoms, type of symptoms, or treatment on the prognosis of patients with primary adenocarcinoma of the lacrimal gland. Our study emphasizes the clinical course, management, and prognosis of 13 patients with primary adenocarcinoma of the lacrimal gland. Most of our patients had a mass in the superotemporal orbit. Proptosis and pain also were common manifestations; however, erythema of the eyelid, lacrimation, or other signs of inflammation were not. Exenteration followed by radiation therapy seems to be the most effective treatment for primary adenocarcinoma of the lacrimal gland. Seven patients received this treatment, four (57%) of whom are the only patients alive without recurrence. One other patient who received this type of treatment is alive but with evidence oflocal spread of tumor, and two patients have died with metastases despite this treatment. No other therapy given to the patients in this series was as effective as exenteration followed by radiation therapy. Four patients who refused further surgery after the diagnosis was made and who subsequently underwent radiation therapy alone have either died (cases 10, 11, and 12) or are alive with evidence of persistent tumor (case 5). One patient who underwent only en bloc resection of his tumor (case 9) died of metastases 7 months later; however, he had evidence of metastases at the time the tumor was first diagnosed and exenteration, therefore, was not performed. One patient (case 7) was treated with exenteration alone. He is alive but has evidence of recurrent tumor. In general, it appears that with shorter duration of symptoms before treatment, metastases are less likely to develop and the chance for long-term survival is greater. Seven patients underwent definitive treatment consisting of exenteration and radiation therapy. The four patients who are alive without evidence of recurrence had symptoms for 9 months or less before they underwent this treatment. One of the two patients who died despite this treatment had symptoms for 8 years before treatment and the other patient had symptoms for 1 year before treatment. In one patient who had symptoms for only 1 month before this treatment, local spread of tumor has developed, but there is no evidence of metastases. Primary adenocarcinoma of the lacrimal gland is not inevitably fatal if diagnosed early and treated appropriately. Four of our patients are alive without evidence of recurrence at least 1 year after treatment. Three of these patients have been tumor-free for 31/2, 14, and 16 years, respectively. Based on our findings, we believe that most patients with signs and symptoms of a lacrimal gland mass, particularly those without evidence of inflammation,

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should have a biopsy performed as soon as possible. For the best chances of survival, primary adenocarcinoma of the lacrimal gland should be treated with exenteration and radiation therapy as soon as a diagnosis is confirmed pathologically. Acknowledgments. The following ph ysicians have

contributed cases to this study: Elson Craig, MD, Joseph Mauriello, MD, Mark Levine, MD, Richard Dortzbach, MD, Gerald Harris, MD, Bartley Frueh, MD, Stephen Trokel, MD, Richard Lisman, MD, J. Brooks Crawford, MD, Ed Howes, MD, John Gamel, MD, Jean Campbell, MD, James Garritty, MD, Winston Harrison, MD, Robert Peiffer, MD, Robert Shaver, MD, Stephen Trokel, MD, Michael Kazim, MD, Allen Putterman, MD, Alan McNab, MD, Arthur Grove, MD, RN Rao, MD.

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References 1. Henderson JW, Neault RW. En bloc removal of intrinsic

2. 3. 4. 5.

neoplasms of the lacrimal gland. Am J Ophthalmol 1976;82: 905-9. Font RL, Gamel JW. Epithelial tumors of the lacrimal gland: an analysis of 265 cases. In: Jakobiec FA, ed. Ocular and Adnexal Tumors. Birmingham: Aesculapius, 1978;787-805. Henderson JW. Orbital Tumors, 2nd ed. New York: B C Decker, 1980;394-424. Wright JE. Factors affecting the survival of patients with lacrimal gland tumours. Can J OphthalmoI1982;17:3-9. Brada M, Henk JM. Radiotherapy for lacrimal gland tumours. Radiother Oncol 1987;9: 175-83.