Poster Design & Printing by Genigraphics® - 800.790.4001

Educational Objective: At the conclusion of this presentation, the participants should be able to describe the cytologic findings of phosphaturic mesenchymal tumor--mixed connective tissue variant as observed in the head and neck.Objectives: To present the first cytologic description of phosphaturic mesenchymal tumor--mixed connective tissue variant in the head and neck.Study Design: Case report.Methods: Radiology, pathology and clinical findings of the first report of phosphaturic mesenchymal tumor--mixed connective tissue variant of the parotid are discussResults: The first report of the cytologic and histologic characteristics of phosphaturic mesenchymal tumor--mixed connective tissue variant of the parotid are described. The paraneoplastic syndrome of oncogenic osteomalacia is also describeConclusions: Fine needle aspiration is often one of the first diagnostic tests performed in the evaluation of a new mass in the parotid area and many other areas within the head and neck. Precise diagnosis of spindle-cell lesions based on fine needle aspirate is extremely challenging, and maintaining a broad cytologic differential diagnosis is paramount. We report the cytologic findings of phosphaturic mesenchymal tumor--mixed connective tissue variant, presenting as an asymptomatic parotid mass. To our knowledge, thisrepresents the first cytologic description within the head and neck literature.

Phosphaturic mesenchymal tumor – mixed connective tissue variant in the parotid gland: Report of a case and discussion of cytologic findings.

Ryan Winters, M.D.1, Kelly Butnor, M.D.2, Abdelmonem Elhosseiny, M.D.21)Tulane University Department of Otolaryngology - Head & Neck Surgery

2) The University of Vermont Department of Pathology

Phosphaturic mesenchymal tumor mixed connective tissue type (PMTMCT) is an extremely rare tumor of soft tissue which is typically associated with oncogenic osteomalacia (OO). Classic histologic features of PMTMCT include osteoclast-like giant cells, spindle to stellate primitive mesenchymal cells, microcysts, and prominent vascularity, both blood vessels and lymphatics1-4.

The presence of both multinucleated giant cells and prominent vasculature (the latter resembling hemangiopericytoma) have often been cited as critical histologic features suggesting the diagnosis of PMTMCT in tissue specimens2,3. As in this case, multinucleated giant cells (MNGC) may appear in the FNA specimen along with connective tissue fragments, and their presence provides a clue to the diagnosis of PMTMCT, so long as they are taken within the context of other cells found within the aspirate. Multinucleated giant cells can be found in a variety of conditions, benign and malignant, neoplastic and reactive; again, it is the remainder of the smear, the context in which they occur that will help narrow the differential diagnosis. MNGC may be seen in granulomatous processes; however the background will be of inflammatory cells, possibly with granulomas themselves seen in the smear7.

Likewise, MNGC may be present in a variety of neoplastic processes, each with characteristic cell types seen in association. Giant cell tumors of bone or of soft tissue may contain osteoclast-like MNGC, but will also demonstrate tumor cells in the smear, it has been postulated that perivascular clumps of tumor cells in association with MNGC are suggestive of giant cell tumor of bone8,9. It is possible that MNGC with connective tissue may be observed in other processes besides PMTMCT. Giant cell fibroblastoma10 may present a similar picture, though this tumor tends to occur in the pediatric population. In the initial cytologic description of PMTMCT by Policarpio-Nicolas, et al.11, similar cytologic findings were described, including single and grouped spindle cells, fibrillary supporting matrix, and very mild cytologic atypia. In addition, this initial report also described overlapping, elongated, tapering nuclei to the tumor cells, some of which appeared to be breaking off of the three-dimensional clusters of cells in the specimen. Plasmacytoid-like cells were also present in their specimen, though they did not observe MNGC in their cytologic specimen. Also, some differences may relate to the cellular makeup of the tumor in the area biopsied. An FNA of the more myxoid areas of tumor with loosely packed spindle cells could appear different from an FNA of more dense areas with osteoclast-like giant cells.

Immunohistochemical studies have shown PMTMCT to be positive for S-100 (as in this study), desmin, chromogranin, FGF-23, CD34, neuron-specific enolase, leukocyte common antigen, Factor VIII-related antigen, and various cytokeratins (though negative for AE1/AE3 in this study)1,3,11. The vast majority of PMTCT will cause some degree of OO through a mechanism thought to involve increased FGF-23, which inhibits phosphate transport in the kidney, and at least one study found that circulating FGF-23 levels returned to within the normal range after resection of PMTMCT12. Antibodies to FGF-23 have been shown to be of diagnostic value in PMTMCT1, though were unavailable to us at the time of diagnosis in this case. It is important to remember that PMTMCT can, very rarely, exist without concurrent OO1,13, and it is unclear if FGF-23 would be elevated in these instances.

This case represents the first cytologic description of PMTMCT in the head and neck to our knowledge, however with such variety of cell types comprising this tumor, precise diagnosis from FNA would be extremely challenging. While diagnosis of soft tissue tumors based on FNA is certainly possible in the hands of an experienced cytopathologist, with some series reporting successful subtyping of up to 83% of malignant lesions and 72% of benign masses5, FNA is more commonly employed to distinguish benign from malignant lesions, where success rates are much higher (92-100%)5,6. In this case, FNA served to exclude malignancy but definitive diagnosis was established on tissue section after surgical excision. It is important for pathologists to include rare entities such as PMTMCT in the differential diagnosis of benign soft tissue tumors with MNGC, or even certain inflammatory processes, when confronted with such an aspirate. This is particularly relevant in cases such as this where no paraneoplastic syndrome was clinically evident

A 55 year-old Caucasian woman presented for evaluation of an asymptomatic left preauricular mass developing over the past month. Physical examination, including cranial nerve examination, was entirely normal except for a firm, fixed, 2cm mass in the left preauricular area. Ultrasound of this nodule demonstrated a heterogeneous mass with no areas of fluid or necrosis, which blended into surrounding parotid tissue. Doppler examination showed the mass to be avascular. Past medical history was significant for total thyroidectomy three months prior for multinodular goiter, which revealed multifocal micropapillary carcinoma, hypertension, osteopenia, and bipolar disorder treated with Lithium for 15 years. Fine-needle aspirate (FNA) of the mass (Figure 1) was overall paucicellular, with multinucleated giant cells, degenerated fibroconnective tissue, bland-appearing spindle cells singly and in groups, and lymphoid cells and blood. No malignant cells were identified, and cells showed neither severe nuclear atypia, nor prominent nucleoli.

Over the next month, the mass increased to 3cm in size and an open biopsy was performed. Histology showed nodules of myxoid material with occasional spindle and stellate cells, interposed with more cellular areas and rare multinucleated giant cells (Figure 2). The spindle cells stained positive for smooth muscle actin (Sigma, clone 1A4) and CD68 (Dako, clone KP1), and the stellate cells were S-100 (Dako, polyclonal) positive, the myxoid areas were negative for keratin staining (Chemicon International, clone AE1/AE3). Imaging with positron-emission tomography (PET) CT was indeterminate, while MRI demonstrated a well-demarcated, T1 isointense and T2 hyperintense, homogeneously enhancing mass in the left anterosuperior parotid (Figure 3). The patient subsequently underwent superficial parotidectomy, which was well-tolerated, for definitive diagnosis and treatment.

INTRODUCTION

1. Folpe, AL, Fanburg-Smith, JC, Billings, SD, et al. Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity. An analysis of 32 cases and a comprehensive review of the literature. Am J Surg Pathol 2004;28(1):1-30.

2. Wakely, PE, Jr., Kneisl, JS. Soft tissue aspiration cytopathology. Cancer2000;90(5):292-8.

3. S i, Z, Antal, I, P ai, Z, et al. Diagnosis of soft tissue tumors by fine-needle aspiration with combined cytopathology and ancillary techniques. Diagn Cytopathol 2002;26(4):232-42.

4. Tse, GMK, Poon, CSP, Law, BKB, et al. Fine needle aspiration cytology of granulomatous mastitis. J Clin Pathol 2003;56(7):519-21.

5. Vetrani, A, Fulciniti, F, Boschi, R, et al. Fine-needle aspiration biopsy diagnosis of giant cell tumor of bone. An experience with nine cases. Acta Cytol 1990;34(6):863-7.

6. Beal, M, Mayerson, J, Wakely, PE, Jr. Fine-needle aspiration cytology of giant cell tumor of soft tissue (soft tissue giant cell tumor of low malignant potential). Ann Diagn Pathol 2003;7(6):365-9.

7. Maitra, A, Timmons, CF, Siddiqui, MT, et al. Fine-needle aspiration biopst features in a case of giant cell fibroblastoma of the chest wall. Arch Pathol Lab Med 2001;125(8):1091-4.

8. Policarpio-Nocolas, M.L., Abbott, T.E., Dalkin, A.C., Bennett-Wick, J., Frierson, H.F. Phosphaturic mesenchymal tumor diagnosed by fine-needle aspiration and core biopsy: A case report and review of the literature. Diagn Cytopathol 2008;36(2):115-9.

9. Jonsson, K.B., Zahradnik, R., Larsson, T., et al. Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. N Engl J Med 2003;348:1656-63.

CONCLUSIONS

DISCUSSIONRESULTS

REFERENCES

ABSTRACT

Ryan Winters, M.D.Tulane University Department of Otolaryngology - Head & Neck SurgeryEmail: rwinters@tulane.eduPhone: (504) 988-5454

CONTACT

Figure 1: A) Degenerated connective tissue with grouped bland stellate to spindle cells, note individual spindle cells apparently fragmenting off of main cluster. B) Individual stellate cell (arrow) broken away from cluster in a background of red blood cells, degenerated connective tissue, and plasmacytoid cell (arrowhead). C) Multinucleated giant cell amidst individual degenerated connective tissue cells, lymphoid cells and red blood cells.

Figure 2: A) Hematoxylin & eosin stained section of tumor mass. Note background of bland stellate and spindle cells with grungy to myxoid matrix and multinucleated giant cells (arrow). B) Representative section of membranous ossification found near periphery of tumor.

Figure 3: Axial MRI showing mass located in left parotid (arrows), isointense on T1 (A) and hyperintense on fat-saturated T2 (B). PET-CT was inconclusive, note some increased uptake in left parotid (arrowhead), however this was not elevated enough to definitively classify as abnormal (C).