A 52-year-old man presents to the clinic with a 2-year history of progressive, severe proximal muscle weakness, deep bone pain, and multiple atraumatic rib fractures. Laboratory evaluation reveals the following:
| Laboratory Test | Result | Reference Range |
|---|---|---|
| Serum calcium | 9.2 mg/dL | 8.4-10.2 mg/dL |
| Serum phosphorus | 1.4 mg/dL | 2.5-4.5 mg/dL |
| Alkaline phosphatase | 285 U/L | 40-120 U/L |
| 25-hydroxyvitamin D | 34 ng/mL | 20-50 ng/mL |
| Intact PTH | 45 pg/mL | 15-65 pg/mL |
| FGF23 | 450 RU/mL | < 180 RU/mL |
A whole-body somatostatin receptor PET/CT scan demonstrates an intensely avid, 2.5-cm soft tissue mass in the plantar aspect of his left foot. The patient undergoes a wide local excision of the lesion.
Which of the following pathologic and immunohistochemical findings are characteristic of this patient's most likely diagnosis? (Select all that apply)
- The presence of bland, uniform spindle cells embedded in a distinctive 'grungy', basophilic, calcified matrixCevap
- Diffuse immunohistochemical expression of fibroblast growth factor 23 (FGF23) and somatostatin receptor 2A (SSTR2A)Cevap
- CNuclear expression of STAT6 and widespread CD34 positivity, indicative of a paraneoplastic syndrome driven by insulin-like growth factor 2
- DHistologic features consistent with a chief cell adenoma, explaining the hypophosphatemia through an ectopic hormone mechanism
- EA biphasic proliferation of epithelial glandular structures and a uniform spindle cell stroma that strongly expresses TLE1
Cevap
The correct findings include the presence of bland spindle cells in a distinctive 'grungy', basophilic, calcified matrix, as well as diffuse immunohistochemical expression of FGF23 and SSTR2A.
The patient's clinical presentation of hypophosphatemia, markedly elevated FGF23, and severe osteomalacia in the setting of a somatostatin receptor-avid soft tissue mass is diagnostic of tumor-induced (oncogenic) osteomalacia. This paraneoplastic syndrome is most commonly caused by a phosphaturic mesenchymal tumor (PMT). Histologically, PMTs are characterized by a proliferation of bland, uniform spindle cells embedded in a highly distinctive 'grungy' or flocculent basophilic, calcified matrix. Immunohistochemically, they typically show diffuse expression of FGF23 (which confirms the mechanism of renal phosphate wasting) and somatostatin receptor 2A (SSTR2A) (which explains the intense avidity on somatostatin-receptor functional imaging, such as DOTATATE PET scans).
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Anahtar Kavram
Diagnosis of phosphaturic mesenchymal tumor (PMT) causing oncogenic osteomalacia requires identifying its characteristic histologic finding (grungy calcified matrix) and specific immunohistochemical profile (FGF23 and SSTR2A positivity).