CASE STUDIES

The Nephrologist’s impact in
cancer of unknown primary syndrom

Figure 1
Skeletal scintigraphy of patient A after injection of technetium 99-m methylene diphosphonate: As predominant finding multiple, focal areas of increased uptake especially in ribs and appendicular skeleton were found.

Since an underlying malignant tumour could not be found, both patients were stigmatised as having “cancer of unknown primary” syndrome (CUP syndrome).
However, since several of the scintigraphic lesions turned out to resemble Looser`s zones, an extended blood testing for bone metabolism was performed.

Table 1
Relevant laboratory tests of patients A and B.

Parameter	Normal range	Patient A	Patient B
Total alkaline phosphatase (AP)	40 - 190 U/l	220	234
Serum inorganic phosphate (SPHO)	0.84 – 1.45 mmol/l	0.42	0.49
Urine inorganic phosphate (UPHO)	mmol/l	19.3	17.4
Serum creatinine (SCr)	0.6 – 1.2 mg/dl	1.0	1.5
Urine creatinine (UCr)	mg/dl	76	72
Fractional phosphate excretion FEPHO	5 – 20 %	60	74
Creatinine clearance	80 - 120 ml/min/1,73m2	95	55
25-Hydroxyvitamin D3 (Calcidiol)	7.5 – 49 µg/l	18	24
1,25-Dihydroxyvitamin D3 (Calcitriol)	17 – 53 ng/l	9	21
Bone specific alkaline phosphatase (BAP)	15 – 41 U/l	68	Not measured
Intact parathyroid hormone (iPTH)	10 – 65 ng/l	31	43

Iliac crest bone biopsy was carried out demonstrating a mineralization defect and an increased surface, width and volume of osteoid.
Hence, the diagnosis of osteomalacia secondary to renal phosphate wasting was established.

Question 1 and 2

In patient A, tumour-induced (oncogenic) osteomalacia was the final diagnosis, since the 1,25-dihydroxyvitamin D3 level was markedly reduced with 25-hydroxyvitamin D3 and creatinine clearance being in normal ranges and since no other cause for renal phosphate wasting could be identified.

Question 3

In patient B a 24-hour urinary specimen revealed proteinuria (2980 mg/day), glycosuria, aminoaciduria and renal bicarbonate loss (renal tubular acidosis type II). The gamma-globulin fraction was elevated to 23% (10-19), IgG was 19.2 g/l (7-16) and immunoelectrophoresis showed Bence-Jones proteinuria type IgG kappa (1420 mg/l). On iliac crest biopsy about 10% plasma cells type light chain kappa were seen in bone marrow. Based on these findings, the diagnosis of monoclonal gammopathy with Bence-Jones proteinuria type kappa and secondary Fanconi syndrome was established.

Question 4

In patient A symptomatic therapy with phosphate-substitution (3600 mg per day) and calcitriol (0.75 µg per day) was begun. In patient B therapy with phosphate substitution (3600 mg per day) and bicarbonate was started.

Question 5

In both patients the discomfort improved with therapy. However, a satisfactory result could only be obtained in Patient A. Tumour localisation was not still impossible after follow-up for 24 months. Finally overt multiple myeloma developed in patient B.

 

Reference List

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