Hypercalcemia Caused by Metastatic Adamantinoma: Response to Radiotherapy

Purpose. To describe successful palliation of a patient with metastatic adamantinoma presenting with lung metastases and hypercalcemia resulting from a parathormone-like substance released from the tumor. Methods and materials. 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 hypercalcemia and adamantinoma were reviewed and summarized. Results. After thorough review of the literature we found no prior reports of radiation being used for palliation of hypercalcemia associated with metastatic adamantinoma.We report rapid improvement in symptoms and normalization 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. Discussion. Radiation therapy should be considered as a palliative option for patients who are not surgical candidates presenting with medically refractory hypercalcemia.


Introduction
A d am an tin om a is a rare tu m o r acco u n tin g for approxim ately 0.1± 0.3% of prim ary bone tum ors. 1,2 It is a slow growing tumor and tends to be locally agg re ssive bu t rarely m etastasizes. 3 T he rate o f m etastasis is approxim ately 15± 20% and u sually occurs in the ® rst two years following diagnosis. 4,5 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 23 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.
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 patient's 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.

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 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 diagnosis. 7± 10 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 refractory to other therapy. 11± 14 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 to norm alization of the serum calcium level. 16 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.