Download COTM0814 - California Tumor Tissue Registry

“A 21 y/o Man with a Mass in
the Inguinal Region”
California Tumor Tissue Registry’s
Case of the Month
CTTR COTM Vol. 16:11
August, 2014
www.cttr.org
History: A 21 year old man presented with an 11 month history of a slow growing,
painless subcutaneous mass in the left inguinal area. A pelvic X-ray showed a 7 x 4 x 2.8
cm well circumscribed periarticular calcified mass within the soft tissue of the hip. It
consisted of multiple small calcified nodules. Serum calcium, phosphate and alkaline
phosphatase levels were normal.
The mass was composed of white, granular material surrounded by a fibrous tissue
capsule. The cut surface was hard, calcified, light tan and chalky. Microscopically, it
showed multiple, solitary and confluent nodules of calcification in a matrix of granular
debris (Figs. 1 - 4). Associated were histiocytes, multinucleated giant cells and
fibroblasts (Figs. 5 - 6).
Diagnosis: Tumoral Calcinosis
Huina Zhang, M.D., Ph.D. and Donald R. Chase, M. D.
Department of Pathology and Human Anatomy,
Loma Linda University Medical Center, Loma Linda, California
California Tumor Tissue Registry, Loma Linda, California
Tumoral calcinosis is a rare sporadic or familial entity characterized by abnormal periarticular deposits of calcium hydroxyapatite, most commonly found around major joints,
especially the hips, shoulders, and elbows without any abnormalities in the calcium
metabolism. It was first described by Duret in 1889 and named by Inclan in 1943. These
lesions are predominantly seen during the first two decades of life and are often
multicentric. It occurs as a well-defined pathologic entity in three heterologous groups of
diseases-- sporadic tumoral calcinosis, familial hyperphosphatemic and
normophosphatemic tumoral calcinosis.

The sporadic form presents with a solitary, large, firm subcutaneous calcified
mass around large joints, often attached to tendon or deep fascia without
involving the underlying bone and joints.

The familial hyperphosphatemic and normophosphatemic tumoral calcinosis
forms are extremely rare and transmitted in an autosomal recessive manner with
variable clinical expression. Germline mutations in the GALNT3, FGF23, KL or
SAMD9 gene have been recently described in familial cases. Imaging studies
CTTR’s COTM
August, 2014
Page 1
reveal a subcutaneous conglomerate of multiple, rounded opacities separated by
radiolucent lines imparting a chicken-wire pattern of lucencies with distinct fluid
levels in some of the nodules. Due to a high recurrence rate, treatment is
complete surgical excision.
Grossly, tumoral calcinosis is a poorly-defined, firm, rubbery mass, ranging in size
between 5-15 centimeters. Cut surfaces demonstrate multilocular cystic cavities filled
with yellow-gray, pastry calcareous or chalky, milky material.
Microscopically, the active cellular phase is characterized by a central mass of
amorphous or granular calcified material surrounded by a florid proliferation of
histiocytes, multinucleated giant cells and variable fibrosis. Later, in the inactive phase,
there is merely calcified material surrounded by dense fibrous tissue or a cystic space
surrounded by calcium deposits. Occasional prominent small psammoma-like bodies or
calcospherites are present.
Since calcification and ossification can be seen in many benign and malignant soft tissue
lesions, the differential diagnosis for tumoral calcinosis is broad and includes all tumoral
calcinosis - like lesions or processes that lead to abnormal dystrophic or metastatic
calcium deposition in the soft tissues:
Acral tumoral calcinosis-like lesions consist of multiple cystic or cleft-like spaces
bordered by histiocytes, osteoclast-like giant cells, with a variable inflammatory infiltrate
and containing fibrin, granular calcific debris, and calcospherites. However, this lesion is
small and is often located in tenosynovial/fascial tissue, with occasional dermal or intraarticular involvement. It can be associated with trauma, scleroderma, or long-standing
osteoarthritis.

Dystrophic calcification shows a similar microscopic picture as tumoral
calcinosis, but usually is smaller and is associated with necrosis secondary to
minor injury, ischemic necrosis or a necrotizing infectious process.

Calcifying fibrous pseudotumor is a fibrous, slowly-growing and painless lesion
that most often affects children and young adults. It is a generally wellcircumscribed, non-encapsulated, hypocellular lesion composed of hyalinized
fibrosclerotic tissue with a scattered lymphoplasmacytic infiltrate, sometimes
forming lymphoid follicles as well as bland, sparse and dispersed spindle cells
within the collagen. The characteristic feature is the presence of scattered
psammomatous calcifications.

Chondroma of soft parts may have similar features to tumoral calcinosis.
However, chondroma usually involves the hands and feet and has a larger
component of differentiated cartilage and lacks the amorphous material. The
calcified material is granular, floccular or crystalline and often outlines the
contours of the chondrocytes in a lace-like pattern.
CTTR’s COTM
August, 2014
Page 2

Calcifying aponeurotic fibroma is a rare, slow growing, small (usually less than 3
cm), painless tumor with fibroblasts palisading around chondroid or calcified
nodules, usually in hands and feet of children or young adults. The calcifications
are usually small and vary from fine granules or string-like deposits to large
amorphous masses, often surrounded by radiating columns of chondrocyte-like
cells.

Calcifying tendinitis is a condition in which there are deposits of hydroxyapatite
crystals in tendons, followed by calcification as well as macrophage and giant cell
reaction. The lesion mostly involves tendons of rotator cuff especially that of
supraspinatus.

Calcifying synovial sarcoma. Calcification can be present to a varying degree in
both monophasic and biphasic variants of synovial sarcoma. It may be
inconspicuous and consist of a few small irregularly distributed spherical
concretions, or it may be extensive and occupy a large portion of the neoplasm.
The subset with extensive calcification occurs mainly in the lower extremity and
is slowly-growing. Most synovial sarcomas show immunoreactivity for epithelial
markers (CK and EMA), TLE1, CD99, BCL-2 and calponin. In addition, more
than 90% of synovial sarcoma have a balanced reciprocal non-random
translocation t(X;18)(p11;q11), with fusion of SSX and SS18 (SYT) genes.
In summary, tumoral calcinosis is a benign neoplasm characterized by abnormal periarticular deposits of calcium hydroxyapatite around major joints. Although there are
different familial and sporadic forms, the constellation of morphologic features is fairly
consistent, which is characterized by a central mass of amorphous or granular calcified
material surrounded by a florid proliferation of histiocytes, multinucleated giant cells and
variable fibrosis.
Suggested Reading:
Hornick JL. Practical Soft Tissue Pathology: A Diagnostic Approach. Elsevier.
Laskin WB, Miettinen M, Fetsch JF. Calcareous lesions of the distal extremities
resembling tumoral calcinosis (tumoral calcinosis-like lesions): clinicopathologic study
of 43 cases emphasizing a pathogenesis-based approach to classification. Am J Surg
Pathol 2007;31;15-25.
Carmichael KD, Bynum JA, Evans EB. Familial tumoral calcinosis: a forty-year followup on one family. J Bone Joint Surg Am 2009;91(3):664-71.
Olsen KM, Chew FS. Tumoral calcinosis: pearls, polemics, and alternative possibilities.
Radiographics 2006;26(3):871-85.
Goldblum JR, Folpe AL and Weiss SW. Enzinger & Weiss’s Soft Tissue Tumors: 6th ed.
2014, Elsevier.
CTTR’s COTM
August, 2014
Page 3