Sarcom a (1999) 3, 33 35

O RIG INAL A RT ICLE

H ypercalcem ia caused by m etastatic adam antinom a: response to radiotherapy

JAN ICE A. LYON S, G. THOM AS BUDD & RICHARD L. CROWN OVER
1 2

D epartments of Radiation O ncolog y and Hematology O ncolog y, The Cleveland Clinic Foundation, Cleveland, O hio, USA

A bstract Pur pose . To describe successful palliation of a patient with metastatic adamantinoma presenting with lung m etastases and hypercalcemia resulting from a parathorm one-like substance released from the tumor. M eth ods and mater ials. The records of a patient with a history of a tibial adamantinoma who presented with symptoms of hypercalcemia 20 years after the original surgery, as well as the literature concerning hypercalcem ia and adamantinoma were reviewed and summ arized. Results. After thorough review of the literature we found no prior reports of radiation being used for palliation of hypercalcem ia associated with metastatic adamantinoma. We report rapid improvement in symptoms and norm alization of serum calcium levels following a course of radiation therapy. The patient remains asymptomatic 15 months following radiotherapy despite a gradual return of elevated serum calcium levels. D iscussion. Radiation therapy should be considered as a palliative option for patients who are not surgical candidates presenting with medically refractory hypercalcem ia. K ey words : Adam antinom a, hypercalcem ia, radiation, PTH -like hor m one .

Introduction A d am an tin om a is a rare tu m o r acco u n tin g for 1,2 approxim ately 0.1 0.3% of prim ary bone tum ors. It is a slow growing tumor and tends to be locally 3 agg re ssive bu t rarely m etastasizes. T he rate o f m etastasis is approxim ately 15 20% and u sually 4,5 occurs in the rst two years following diagnosis. T he m ost comm on sites of m etastases are bone, lung, and regional lym ph nodes. 4 Although m any patients w ith osteolytic bony m etastases from other prim ar y tum ors present w ith hyp ercalcemia it is unusual to see hypercalcemia in patients with adam antinom a, especially in the absence of bony disease. Here we present a patient with an adam antinom a of the tibia w ho subsequently developed lung m etastases and severe hypercalcemia. C ase repor t A 39-year-o ld white m ale presented in 1973, at the age of seventeen, w ith a left tibial m ass. Biopsy revealed an adam antinom a. The patient subsequently underwent a below knee am putation. He did well until 1993 w hen he started experiencing increasing weakness and cough. Chest X-ray at that time revealed bilateral pulm onary nodules. Biopsy of a left lung

nodule revealed m etastatic adam antinom a. M agnetic resonance im ag ing (M RI# )0 of the abdom en was n egative but im ages of the ch est revealed a heterogeneous soft tissue m ass in the left hem ithorax enlarging the costophrenic sulcus, probably located in the pleu ral sp ace and con tigu ou s w ith both the diaphragm and visceral pleura of the paraspinal soft tissue. There was also a 2 3 3 cm left anterior chest wall m ass and a right m iddle lobe nodule. The serum calcium was 12.8 m g/dl (normal range 8.5 10.5). He underwent right upper lobectomy and wedge resection of the right m iddle and lower lobes, con r m ing metastatic adamantinoma.This was followed by a wedge resection of the left upper lobe that was negative for neoplasm and resection of tissue adjacent to the aorta which revealed metastatic adamantinoma. The patient was seen in Radiation O ncology following surgical resection; however, due to anticipated high dose and large eld size requirements it was thought that chem otherapy was a better option. H e received six cycles of chemotherapy with m esna, adriamycin, ifosfam ide, and D T IC (M AID ) with granulo c yte co lo ny -stim u latin g fa cto r (G -C S F ) a n d interleukin-6 (IL-6) support from O ctober 1993 to February 1994. This was followed by six cycles of carboplatin from June 1994 to D ecember 1994.

Correspondence to: Richard L. Crownover, Ph.D., M .D., Departm ent of Radiation Oncology, Desk T-28, T he Cleveland Clinic Foundation, Cleveland, OH 44195, U SA. Tel.: (216) 444-1925 ; Fax: (216) 444-5331; email: crownover@radonc.ccf.org 1357-714 X/99/010033-0 3 $9.00 1999 Taylor & Francis Ltd

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J. Lyons et al.

Fig. 1. Var iations in ser um calcium levels dur ing treatm ent.

T he patient was m aintained on pam idronate for chronic tumor related hyp ercalcem ia from April 1996 to D ecem ber 1996 when com puterized tom ography (CT ) scan of the chest revealed a large soft tissue m ass in the left lower lobe of the lung involving the diaph ragm and extending into the abdom en lateral to the spleen. T here was rib involvem ent, displacement of the heart and esophagus to the right, encasem ent of the aorta and com pression of the left atrium . At that time the patient was com plaining of rib pain, dyspnea on exertion, fatigue and constant thirst. His calcium was 15.2 m g/dl. H e was tested for parathorm one related peptide and his serum level was elevated at 9.6 pm ol/l (norm al range 0.0 1.5). T he patient received radiation therapy to the left hem ithorax from Februar y 1997 until M arch 1997. This consisted of 45 G y prescribed to the 98% isodose line via left posterior oblique/left anterior oblique eld ar ran gem en t u sin g 6 an d 10 M V p ho to n s delivered by a linear accelerator equipped with a m ulti-leaf collim ator. A partial transm ission block was effected by varying the leaf positions during treatm ent to lim it the dose to the left ventricle to 36 G y. We used a lung correction factor of 0.33. T he patient tolerated treatm ent well; however, he required a brief hospitalization for atrial brillation and pericarditis toward the end of the course. This resolved during his hospital stay. T he patients energy level increased during the course of treatm ent and his calcium level at com pletion was 11.5 m g/dl. T he patient was able to work full time as a high-level software developer throughout the course of treatment. For 9 m onths fo llow in g treatm en t the p atien t s calciu m level rem ained around the norm al range; however, recently this has started to increase with his last calcium being 14.0 m g/dl (June 1998; Fig. 1) H e continues to work fu ll tim e and is w ithou t co m plain ts 15 m o nths following com pletion of radiation.

recurrence rate if m arginal surgery is perform ed. 6 There have been several reports of patients with lung metastases that develop several years after the original 7 10 diagnosis. Since patients with metastatic disease can still have prolonged sur vival, aggressive therapy is often warranted. H ypercalcem ia is a com m on occurrence in cancer patients. It can result from bone destruction from m etastatic disease or it m ay arise from tum oral secretion of parathorm one-like substances. In som e of these cases radiation therapy has been used sucessfully to control tum or-related hypercalcem ia that is 11 14 refractory to other therapy. T here are reports in the literature of patients with m etastatic am eloblastom a presenting with hypercalcemia; in these cases the hypercalcemia is often associated with high levels of a parathyroid-like horm one circulating in the blood.15 Although this phenom enon is often asso ciated with m etastatic disease, there have been sim ilar cases repor ted in which the prim ary tum or was thought to be producing a parathyroidlike substance. In one case, resection of the tum or led 16 to norm alization of the serum calcium level. Our case dem onstrates that radiation therapy can be used as another m odality to norm alize elevated calcium levels produced by m etastatic adam antinom a and should be considered as a palliative treatm ent option in patients presenting with m edically refractory hypercalcemia who are not surgical candidates. References
1 M irra JM . Adamantinoma and osteo brous dysplasia. In: B one tum ors. clinical, radiolog ic, and patholog ic correlations. Philadelphia: Lea and Febiger, 1989: 1204 31. 2 M oon NF, M ori H. A damantinoma of the append icu lar s keleton u pd ated . C lin O r th op 1986; 204:215 37. 3 Gardner DG, Pecak AM J. The treatment of ameloblastoma based on pathologic and anatomic principles. Cancer 1990; 46:2514 19. 4 Weiss SW, Dorfman M B. Adamantinoma of long bone. An analysis of nine new cases with emphasis on metastasizing lesions and brous dysplasia like changes. H uman Pathol 1977; 8:141 53. 5 Altmannsberger M, Poppe H, Schauer A. An unusual case of adamantinom a of long bones. J Cancer Res C lin O ncol 1982; 104:315 20.

Discussion Adam antinom a (ameloblastom a) is a rare entity that usually arises in the m andible but has been dem onstrated in other bones. T his tum or is considered to be low grade; however, it does tend to have a high local

Radiation for hypercalcemia in metastatic adam antinoma

6 Jundt G, Remberger K, Roessner A, Schultz A, Bohndorf K. Adamantinoma of long bones. A histopathological and imm unohistochemical study of 23 cases. Pathol Res Practice 1995; 191:112 20. 7 Sheppard BC, Temeck BK, Taubenberger JK, Pass HI. Pulmonary metastatic disease in ameloblastoma. Chest 1993; 104:193 3 35. 8 Hazelbag H M , Tam iniau A H, Fleuren GJ, Hogendoorn PC. Adamantinoma of the long bones. A clinicopathological study of thirty-two patients with em phasis on histological subtype, precursor lesion, and biological behavior. J B one Joint Surg Am Vol 1994; 76:1482 99. 9 Inoue N, Shimojyo M , Iwai H, et al. M alignant ameloblastoma with pulmonary metastasis and hypercalcemia. Report of an autopsy case and review of the literature. Am J Clin Pathol 1988; 90:474 81. 10 Harada K, Suda S, Kayano T, Nagura H, Enomoto S. Ameloblastoma with metastasis to the lung and associated hypercalcem ia. J O ral M a xillofac S u rg 19 89 ; 47:1083 87.

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11 Neskovic-Konstantinovic Z, Susnjar S, Vasovic S, et al. Tumour-induced hypercalcemia, resistant to systemic anti-hypercalcemic and chem-endocrine treatments, but responding to radiotherapy in a breast cancer patient. A cta O ncol 1996; 35:501 503. 12 Suzuki K, Tanaka H, Shibusa T, et al. Parathyroidhormone-related-protein-producing thymic carcinoma presenting as a giant extrathoracic mass. Respiration 1998; 65:83 85. 13 Al-Rashid RA, Cress C. Hypercalcem ia associated with neuroblastoma. Am J Dis Child 1979; 133:838 841. 14 B akri Y N , A kh tar M . G on ad al d ys germ ino m aseminoma associated with severe hypercalcemia. Acta O bstet Gynecol Scand 1993; 72:57 59. 15 M adiedo G, C hoi H, Kleinman JG. Ameloblastoma of the maxilla with distant metastases and hypercalcem ia. A m J C lin Pathol 1981; 75:585 91. 16 M cGuirt W F, Scruggs MS, Koufman JA. Hypercalcem ia secondary to a pseudoparathormone-secreting ameloblastoma. A rch Otola r yngol 1981; 107:487 90.