Clinical, histopathologic, subtype, and immunohistochemical analysis of jaw phosphaturic mesenchymal tumors

Abstract

Jaw phosphaturic mesenchymal tumors (PMTs) are a rare neoplasm with uncertain histogenesis. This study aimed to clarify the clinical and pathological features of jaw PMTs.We reviewed the clinical records of 39 patients diagnosed with PMTs in the jaws, and investigated clinical and morphologic characteristics, histologic subtypes, and immunophenotypes of all cases.Microscopic analyses revealed 2 major histologic tumor subtypes: "phosphaturic mesenchymal tumors of mixed epithelial and connective tissue" (PMTMECT), and "phosphaturic mesenchymal tumors of mixed connective tissue" (PMTMCT). PMTMECTs and PMTMCTs accounted for 29 and 10 cases of PMTs, respectively. Most PMTMECT diagnoses were made predominantly in males aged <45 years, and the incidence was similar in both the mandible and maxilla. In contrast, patients with PMTMCTs are predominantly females aged ≥45 years, and all tumors were in the mandible. Histologically, PMTMECT had lower cellularity and a more elongated and spindled mesenchymal component with less elaborate intrinsic microvasculature than PMTMCT. Immunohistochemically, the epithelia of all PMTMECTs was immunoreactive for AE1/AE3. Other immunohistochemical staining of PMTMECTs revealed positive expression of vimentin, SATB2, ERG, CD99, Bcl-2, CD56, S-100, D2-40, CD68, SMA, and CD34 in either one or both components. Immunohistochemical staining of PMTMCTs was diffusely positive for vimentin and a varied ratio of positivity for SATB2, ERG, CD99, Bcl-2, CD56, S-100, D2-40, CD68, SMA, and CD34, but negative for AE1/AE3. Most patients were cured by complete resection, except 2 patients who had repeated recurrences, one of which also had multiple metastasis.Jaw PMT can be divided into 2 major histological subtypes. PMTMECTs are more common than are PMTMCTs, and can transform into malignant PMTMCTs during the progression. PMTMECTs were more commonly observed in males and the incidence was similar in both the maxilla and mandible. PMTMCTs were almost always observed in the mandible of females. Compared with PMTMCTs, PMTMECTs have an admixture of epithelial components with less prominent vasculature and lower cellularity. There were no statistically significant differences in the expression of immunohistochemical markers except AE1/AE3 between PMTMECTs and PMTMCTs. However, immunohistochemical markers have great significance for differentiating other mesenchymal tumors.

Figure 1

The anatomical site distribution of 289 PMTs.

Figure 2

Octreotide scanning was performed in a 31-year-old man who presented with osteomalacia for 2 years. The maximum intensity projection (MIP) image (lower left) reveals a small focus of high somatostatin receptor expression in the left mandible.

Figure 3

A. The tumor destroys the trabecular meshwork and infiltrates into the surrounding soft tissue and oral mucosa focally (under low magnification). B. PMTMECT contains an admixture of neoplastic epithelial and mesenchymal elements with less prominent vasculature and lower cellularity compared with typical PMTMCT. The mesenchymal component exhibits a more elongated and spindled morphology. The epithelial component of PMTMECT is composed of haphazard and diffuse small, irregular nests throughout the tumor which morphologically resemble odontogenic epithelial nests. Focal osteoid matrix and abnormal thick-walled vessels are present. C. PMTMCT is composed of round to oval, or stellate to spindle, primitive mesenchymal cells. Abnormal thick-walled vessels are readily visible. D. The cytoplasm of PMTMECT is eosinophilic or clear and the nuclei are evenly distributed and unpolarized in neoplastic epithelial cells. E. “Grungy” calcification of PMTMECT. F. Osteoclast-like giant cells are seen in PMTMECT with focal areas of hemorrhages. G. PMTMCT focal osteoid matrix. H Perivascular myxoid changes and “grungy” calcification of PMTMCT. I. Normochromatic nuclei and inconspicuous nucleoli in PMTMCT tumor cells.

Figure 4

All components are positive for FGF23 (A) and NSE (B). The epithelial and mesenchymal components of PMTMECT show strong diffuse immunoreactivity for AE1/AE3 (C) and vimentin (D), respectively. Most cases are variably positive for CD99 (E), Bcl-2 (F) and CD56 (G) in both components, and the epithelial component exhibits stronger and more diffuse immunoreactivity for FGF23, NSE, CD99, Bcl-2, and CD56 than do the paired connective tissue components. Diffuse or variable focal positive staining for CD68 (H) and SATB2 (I).

Figure 5

PMTMCT is variably, but diffusely, positive for vimentin (A), CD99 (B), Bcl-2 (C), CD56 (D), and S-100 (E), and focally positive SATB2 (F), ERG (G), SMA (H), and CD34 (I).