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Among all orbital masses in children, tumors and related lesions ofthe lacrimal gland are very uncommon (1.8%-2.4%). Most of these prove to benongranulomatous or granulomatous chronic dacryoadenitis, with only a fewbeing 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 commonin adults but very rare in children. In published series of orbital massesin children by Shields et al1 and Kodsiet al,2 340 and 250 masses, respectively,included no case of PALG. We are aware of only 4 cases reported in childrenaged 14 years or younger and another 3 cases reported in adolescents, withthe first being reported in 1938 by Sanders3 andwith a 6-year-old boy as the youngest patient at the time of diagnosis.4 Mercado et al5 reportedthe case of a PALG in a 15-year-old girl. None of these cases had any historyof chemotherapy or radiotherapy for leukemia or any deficiency of the immunesystem.
Report of a Case
We herein describe a 14-year-old white girl who was initially examinedat our clinic because of a swelling of the upper lid that increased for 3years. The medical history disclosed that the girl was in first remissionafter therapy for acute lymphoblastic leukemia (ALL) following a Berlin-Frankfurt-Münsterregimen 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 thetemporal half of the superior orbital rim with mild ptosis of the right eye(Figure 1A).
A, Frontal view of our patientshowing swelling of the right upper lid. B, Magnetic resonance image showsa multicystic contrast-positive tissue enlargement in the lacrimal fossa.
The globe was displaced downward with a restriction of elevation. Thepatient experienced no pain. Visual acuity, intraocular pressure, and resultsof ophthalmoscopic assessment were normal.
Magnetic resonance imaging showed a multicystic contrast-positive enlargementof 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 asuperior orbitotomy, we found an encapsulated solid nodule in the lacrimalfossa closely associated with the lacrimal gland. The noninvasive tumor wasexcised completely within its intact capsule. The specimen measured 3.4 ×2.2 × 1.6 cm (Figure 2A).
A, Excised mass with intact capsule.B, The lacrimal pleomorphic adenoma has a thin fibrous and inflamed capsuleseparating the tumor from the gland. The anastomosing trabeculae of cordlikeepithelial cells show sparse well-formed ductal or tubular structures thatare closely associated with an interposed stromal component. This mesenchymalcomponent of the pleomorphic adenoma contains some stellate mesenchymal cells.Bleeding and necroses are not evident (hematoxylin-eosin, original magnification×100). C, Area of the chondroid matrix containing groups of ballooncells similar to chondrocytes. A well-defined border delimits this area. Thecell-rich epithelial component consists of monomorphic cells with a completeabsence of stroma. Nuclear irregularities were absent (alcian blue, originalmagnification ×400).
During a 2-year follow-up, the patient showed no signs of recurrence.
Histologically the capsulated tumor consisted of epithelial and mesenchymal-liketissues (Figure 2B). The epithelialcomponent consisted of nests and cords of monomorphic cells, some of whichwere arranged in tubules containing protein that was positive for periodicacid–Schiff stain. Myoepithelial cells within the epithelial cords couldnot be detected immunohistochemically by antibodies against smooth-muscleactin. We found no nuclear irregularity or mitosis. The second component ofthe tumor consisted of a myxoid and chondroid matrix containing mesenchymalcells that resembled chondrocytes and were positive for alcian blue stain(Figure 2C). There were no signsof a relapsed ALL.
The histopathologic diagnosis was of a myxochondromatous variation ofa PALG.
The appropriate therapy for PALG is surgical excision.6 Ifsuch tumors are excised completely within their capsules, the 5-year recurrencerate is 3%, compared with 32% if the tumors undergo biopsy before removal.Rupture of the capsule of a PALG affects the prognosis adversely because ofseeding 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 10years after B-cell–type ALL. At 4 years of age, she received chemotherapythat included daunorubicin, doxorubicin, cyclophosphamide, and methotrexate.Cranial irradiation (1200 rad) was given for prophylaxis of the central nervoussystem.
The treatment of children with ALL is increasingly successful, witha current overall survival rate of almost 80%. However, the immunosuppressiveand cytotoxic therapy necessary to achieve this improvement increases therisk of subsequent complications. There is a 14-fold increase in the incidenceof secondary neoplasma after therapy for ALL. The cumulative risk of secondaryneoplasms in first complete remission ranges from 1.9% to 2.9% by 15 to 20years.8,9
The literature contains no report of an association between chemotherapyor irradiation and the incidence of PALG. However, there is evidence thatsalivary gland tumors can be caused by therapeutic irradiation of the headin childhood, with a long latency and in a dose-response manner.10,11 A2.6-fold incidence of benign mixed tumors (pleomorphic adenomas) or a 4.5-foldincidence of malignant neoplasia of the salivary gland was noted in a cohortof patients who received 350-rad irradiation of the head for tinea capitisin childhood.12
It is therefore possible that the development of PALG, which shows clinicaland histological similarity to the salivary gland tumors mentioned in thepreceding paragraph, was influenced by irradiation and chemotherapy for ALLin our case.
The increasing number of children surviving ALL indicates a need forawareness 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, Domagkstr15, 48129 Münster, Germany.
The authors have no relevant financial interest in this article.
Stupp T, Pavlidis M, Buchner TF, August C, Busse H. Pleomorphic Adenoma of the Lacrimal Gland in a Child After Treatmentof Acute Lymphoblastic Leukemia. Arch Ophthalmol. 2004;122(10):1538–1540. doi:10.1001/archopht.122.10.1538
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