December Case of the Month – 47 y/o male with shoulder mass

This will likely mark the last post for 2008 for a brief hiatus over the holidays. I would like to thank all my colleagues and readers for your continued support. I would also like to thank Aperio who have generously sponsored and supported this endeavor to support educational initiatives in digital pathology and pathology informatics through the blog this past year. Best wishes for a happy holiday season. Keith 

The Case of the Month for December is from a right shoulder mass in a 47 year old male. While the cytogenetic abnormalities have not been described in this entity, we had the opportunity to collect fresh tissue for cytogenetic studies from the surgical specimen at the time of frozen section. The results of those studies are shown here:  

46,XY,add(2)(q31),add(4)(q31.1)[2]/92,slx2[3]/46,sl,

der(2)t(2;4)(q14.2;p14),

der(4)t(2;4)(q14.2;p14)add(4)(q31.1)[10]/46,sdl1,

add(13)(q34)[4]/92,sdl2x2[1] 

The vast majority of the tumor showed low overall cellularity with bland appearing cells, myxoid change, distinctive “grungy” calcified matrix, and rare osteoclasts. 

The diagnosis and a reference are below the images.

Enjoy!

Diagnosis:

Phosphaturic mesenchymal tumor (mixed connective tissue variant) (PMTMCT). 

Reference:

Am J Surg Pathol. 2004 Jan;28(1):1-30.

Most osteomalacia-associated mesenchymal tumors are a single histopathologic
entity: an analysis of 32 cases and a comprehensive review of the literature.

Folpe AL, Fanburg-Smith JC, Billings SD, Bisceglia M, Bertoni F, Cho JY, Econs
MJ, Inwards CY, Jan de Beur SM, Mentzel T, Montgomery E, Michal M, Miettinen M,
Mills SE, Reith JD, O’Connell JX, Rosenberg AE, Rubin BP, Sweet DE, Vinh TN, Wold
LE, Wehrli BM, White KE, Zaino RJ, Weiss SW.

Oncogenic osteomalacia (OO) is a rare paraneoplastic syndrome of osteomalacia due
to phosphate wasting. The phosphaturic mesenchymal tumor (mixed connective tissue
variant) (PMTMCT) is an extremely rare, distinctive tumor that is frequently
associated with OO. Despite its association with OO, many PMTMCTs go unrecognized
because they are erroneously diagnosed as other mesenchymal tumors. Expression of
fibroblast growth factor-23 (FGF-23), a recently described protein putatively
implicated in renal tubular phosphate loss, has been shown in a small number of
mesenchymal tumors with known OO. The clinicopathological features of 32
mesenchymal tumors either with known OO (29) or with features suggestive of
PMTMCT (3) were studied. Immunohistochemistry for cytokeratin, S-100, actin,
desmin, CD34, and FGF-23 was performed. The patients (13 male, 19 female) ranged
from 9 to 80 years in age (median 53 years). A long history of OO was common. The
cases had been originally diagnosed as PMTMCT (15), hemangiopericytoma (HPC) (3),
osteosarcoma (3), giant cell tumor (2), and other (9). The tumors occurred in a
variety of soft tissue (21) and bone sites (11) and ranged from 1.7 to 14 cm.
Twenty-four cases were classic PMTMCT with low cellularity, myxoid change, bland
spindled cells, distinctive “grungy” calcified matrix, fat, HPC-like vessels,
microcysts, hemorrhage, osteoclasts, and an incomplete rim of membranous
ossification. Four of these benign-appearing PMTMCTs contained osteoid-like
matrix. Three other PMTMCTs were hypercellular and cytologically atypical and
were considered malignant. The 3 cases without known OO were histologically
identical to the typical PMTMCT. Four cases did not resemble PMTMCT: 2 sinonasal
HPC, 1 conventional HPC, and 1 sclerosing osteosarcoma. Three cases expressed
actin; all other markers were negative. Expression of FGF-23 was seen in 17 of 21
cases by immunohistochemistry and in 2 of 2 cases by RT-PCR. Follow-up (25 cases,
6-348 months) indicated the following: 21 alive with no evidence of disease and
with normal serum chemistry, 4 alive with disease (1 malignant PMTMCT with lung
metastases). We conclude that most cases of mesenchymal tumor-associated OO, both
in the present series and in the reported literature, are due to PMTMCT. Improved
recognition of their histologic spectrum, including the presence of bone or
osteoid-like matrix in otherwise typical cases and the existence of malignant
forms, should allow distinction from other mesenchymal tumors. Recognition of
PMTMCT is critical, as complete resection cures intractable OO.
Immunohistochemistry and RT-PCR for FGF-23 confirm the role of this protein in
PMTMCT-associated OO.