 |
|
Pleomorphic Adenoma of the Lacrimal Gland in a Child After Treatment of Acute Lymphoblastic Leukemia
Arch Ophthalmol. 2004;122:1538-1540.
Among all orbital masses in children, tumors and related lesions of the lacrimal gland are very uncommon (1.8%-2.4%). Most of these prove to be nongranulomatous or granulomatous chronic dacryoadenitis, with only a few being neoplasms.1
Pleomorphic adenoma (benign mixed tumor) of the lacrimal gland (PALG) is a benign tumor that mostly arises in the orbital lobe. It is quite common in adults but very rare in children. In published series of orbital masses in children by Shields et al1 and Kodsi et al,2 340 and 250 masses, respectively, included no case of PALG. We are aware of only 4 cases reported in children aged 14 years or younger and another 3 cases reported in adolescents, with the first being reported in 1938 by Sanders3 and with a 6-year-old boy as the youngest patient at the time of diagnosis.4 Mercado et al5 reported the case of a PALG in a 15-year-old girl. None of these cases had any history of chemotherapy or radiotherapy for leukemia or any deficiency of the immune system.
Report of a Case
We herein describe a 14-year-old white girl who was initially examined at our clinic because of a swelling of the upper lid that increased for 3 years. The medical history disclosed that the girl was in first remission after therapy for acute lymphoblastic leukemia (ALL) following a Berlin-Frankfurt-Münster regimen that included daunorubicin hydrochloride, doxorubicin hydrochloride, cyclophosphamide, and methotrexate disodium. Cranial irradiation (1200 rad) was given for prophylaxis of the central nervous system.
Ophthalmological examination showed a palpable nodular mass under the temporal half of the superior orbital rim with mild ptosis of the right eye (Figure 1A).
|
|
|
|
Figure 1. A, Frontal view of our patient showing swelling of the right upper lid. B, Magnetic resonance image shows a multicystic contrast-positive tissue enlargement in the lacrimal fossa.
|
|
|
The globe was displaced downward with a restriction of elevation. The patient experienced no pain. Visual acuity, intraocular pressure, and results of ophthalmoscopic assessment were normal.
Magnetic resonance imaging showed a multicystic contrast-positive enlargement of tissue in the lacrimal fossa. There were no signs of osseal destruction (Figure 1B).
We decided to perform surgical excision of the orbital mass. After a superior orbitotomy, we found an encapsulated solid nodule in the lacrimal fossa closely associated with the lacrimal gland. The noninvasive tumor was excised completely within its intact capsule. The specimen measured 3.4 x 2.2 x 1.6 cm (Figure 2A).
|
|
|
|
Figure 2. A, Excised mass with intact capsule. B, The lacrimal pleomorphic adenoma has a thin fibrous and inflamed capsule separating the tumor from the gland. The anastomosing trabeculae of cordlike epithelial cells show sparse well-formed ductal or tubular structures that are closely associated with an interposed stromal component. This mesenchymal component of the pleomorphic adenoma contains some stellate mesenchymal cells. Bleeding and necroses are not evident (hematoxylin-eosin, original magnification x100). C, Area of the chondroid matrix containing groups of balloon cells similar to chondrocytes. A well-defined border delimits this area. The cell-rich epithelial component consists of monomorphic cells with a complete absence of stroma. Nuclear irregularities were absent (alcian blue, original magnification x400).
|
|
|
During a 2-year follow-up, the patient showed no signs of recurrence.
Histopathologic Findings
Histologically the capsulated tumor consisted of epithelial and mesenchymal-like tissues (Figure 2B). The epithelial component consisted of nests and cords of monomorphic cells, some of which were arranged in tubules containing protein that was positive for periodic acid–Schiff stain. Myoepithelial cells within the epithelial cords could not be detected immunohistochemically by antibodies against smooth-muscle actin. We found no nuclear irregularity or mitosis. The second component of the tumor consisted of a myxoid and chondroid matrix containing mesenchymal cells that resembled chondrocytes and were positive for alcian blue stain (Figure 2C). There were no signs of a relapsed ALL.
The histopathologic diagnosis was of a myxochondromatous variation of a PALG.
Comment
The appropriate therapy for PALG is surgical excision.6 If such tumors are excised completely within their capsules, the 5-year recurrence rate is 3%, compared with 32% if the tumors undergo biopsy before removal. Rupture of the capsule of a PALG affects the prognosis adversely because of seeding of tumor cells into the surrounding tissues and malignant transformation.7
The etiology of PALG is unknown.
Our patient was initially seen in a condition of first remission 10 years after B-cell–type ALL. At 4 years of age, she received chemotherapy that included daunorubicin, doxorubicin, cyclophosphamide, and methotrexate. Cranial irradiation (1200 rad) was given for prophylaxis of the central nervous system.
The treatment of children with ALL is increasingly successful, with a current overall survival rate of almost 80%. However, the immunosuppressive and cytotoxic therapy necessary to achieve this improvement increases the risk of subsequent complications. There is a 14-fold increase in the incidence of secondary neoplasma after therapy for ALL. The cumulative risk of secondary neoplasms in first complete remission ranges from 1.9% to 2.9% by 15 to 20 years.8-9
The literature contains no report of an association between chemotherapy or irradiation and the incidence of PALG. However, there is evidence that salivary gland tumors can be caused by therapeutic irradiation of the head in childhood, with a long latency and in a dose-response manner.10-11 A 2.6-fold incidence of benign mixed tumors (pleomorphic adenomas) or a 4.5-fold incidence of malignant neoplasia of the salivary gland was noted in a cohort of patients who received 350-rad irradiation of the head for tinea capitis in childhood.12
It is therefore possible that the development of PALG, which shows clinical and histological similarity to the salivary gland tumors mentioned in the preceding paragraph, was influenced by irradiation and chemotherapy for ALL in our case.
The increasing number of children surviving ALL indicates a need for awareness of such neoplasms (which were previously considered to be very rare), comprehensive examination, and long-term follow-up.
Correspondence: Dr Stupp, University Eye Hospital Münster, Domagkstr 15, 48129 Münster, Germany.
The authors have no relevant financial interest in this article.
Tobias Stupp, MD;
Mitrofanis Pavlidis, MD;
Thomas F. Buchner, MD;
Christian August, MD;
Holger Busse, MD
REFERENCES
|
1. Shields JA, Bakewell B, Augsburger JJ, Donoso LA, Bernadino V. Space-occupying orbital masses in children: a review of 250 consecutive biopsies. Ophthalmology. 1986;93:379-384.
ISI
| PUBMED
2. Kodsi SR, Shetlar DJ, Campbell RJ, Garrity JA, Bartley GB. A review of 340 orbital tumors in children during a 60-year period. Am J Ophthalmol. 1994;117:177-182.
ISI
| PUBMED
3. Sanders TE. Mixed tumor of the lacrimal gland. Arch Ophthalmol. 1939;21:239-260.
FREE FULL TEXT
4. Faktorovich EG, Crawford JB, Char DH, Kong C. Benign mixed tumor (pleomorphic adenoma) of the lacrimal gland in a 6-year-old boy. Am J Ophthalmol. 1996;122:446-447.
PUBMED
5. Mercado GJ, Gunduz K, Shields CL, Shields JA, Eagle RC Jr. Pleomorphic adenoma of the lacrimal gland in a teenager. Arch Ophthalmol. 1998;116:962-963.
FREE FULL TEXT
6. Rose GE, Wright JE. Pleomorphic adenoma of the lacrimal gland. Br J Ophthalmol. 1992;76:395-400.
FREE FULL TEXT
7. Font RL, Gamel JW. Epithelial tumours of the lacrimal gland: an analysis of 265 cases. In: Jakobiec FA, ed. Ocular and Adnexal Tumors. New York, NY: Aesculapius Publishers Inc; 1978:787-805.
8. Löning L, Zimmermann M, Reiter A, et al. Secondary neoplasms subsequent to Berlin-Frankfurt-Münster therapy of acute lymphoblastic leukemia in childhood: significantly lower risk without cranial radiotherapy. Blood. 2000;95:2770-2775.
FREE FULL TEXT
9. Neglia JP, Meadows AT, Robison LL, et al. Second neoplasms after acute lymphoblastic leukemia in childhood. N Engl J Med. 1991;325:1330-1336.
ABSTRACT
10. Schneider AG, Favus MJ, Stachura ME, Arnold MJ, Frohman LA. Salivary gland neoplasms as a late consequence of head and neck irradiation. Ann Intern Med. 1977;87:160-164.
11. Katz AD, Preston-Martin S. Salivary gland tumors and previous radiotherapy to the head or neck: report of a clinical series. Am J Surg. 1984;147:345-348.
PUBMED
12. Modan B, Chetrit A, Alfandary E, et al. Increased risk of salivary gland tumors after low-dose irradiation. Laryngoscope. 1998;108:1095-1097.
FULL TEXT
| PUBMED
SECTION EDITOR: W. RICHARD GREEN, MD
|
