October 2014

A 45 year old female with a right foot mass

Derrick Green, MD, Patrick Bacaj, MD

Overview

The patient is a 45 year old female who initially presented to her primary care provider with the chief complaint of a right foot mass. Four months prior to her presentation she sustained a fracture of her right 5th metatarsal. Her entire foot swelled, and after the swelling subsided she noticed a mass on the dorsum of her foot. The patient complained of sharp, burning pain in her foot which was worse at night.

Physical exam revealed a soft, mobile, fluctuant mass on the dorsum of the foot over the head of the third toe. Deep palpation revealed fullness in the mid foot both on the plantar and dorsal aspect in between the second and third metatarsals. The second and third toes had increased interdigital space when compared to the contralateral side and were observed to be diverging. Pain was not elicited upon palpation.

An MRI performed on the right foot showed a homogeneous mass that was hypointense on T1 and hyperintense on T2. The mass appeared to encompass the entire third metatarsal as well as the majority of the second metatarsal. There was a significant increase in signal uptake on T2 in the marrow of the third metatarsal with thinning of the cortex; however, no apparent cortical breakthrough was observed. 

A subsequent CT-guided needle core biopsy was performed; the specimen was diagnosed as malignant. A Lisfranc amputation of the right foot was performed.

Gross Description

Picture 1 and 2 caption: Gross photographs showing the tumor to have a tan-white, fleshy cut surface with focal areas of cystic change. The tumor was intimately associated with both tendon and muscle.

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Picture 3: Photomicrograph showing the spindle cell component with several mast cells.
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Picture 4: Photomicrograph showing the epithelioid component which contains pink, eosinophilic material.
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Picture 5: Brisk mitotic activity was observed in areas containing epithelioid differentiation.
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Picture 6: Photomicrograph of the tissue core biopsy showing the epithelioid component with pink eosinophilic material.

Diagnosis

What is the most likely diagnosis ?

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What is the most likely chromosomal abnormality associated with this entity ?

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Discussion

Synovial sarcoma (SS) is a malignant soft tissue tumor that may display focal epithelial differentiation. It represents roughly 10% of all reported soft tissue sarcomas.[1] The entity synovial sarcoma was so named because it was once believed to recapitulate synovium, but despite its name, SS is not composed of synovial cells. It is a tumor of uncertain histogenesis. Moreover, although the term synovial sarcoma implies an origin from the joint linings, less than 10% are intra-articular.[2]

SS is most prevalent in adolescents and young adults between the ages of 15 and 40 years. Males are slightly more frequently affected than females with a ratio of 1.2:1.[1,3,4] It may occur in virtually any location including the viscera, but most often is found around large joints, especially the knee region.[2] In most cases, it will display both a spindle cell component and an epithelial component.[1,3,4] SS typically presents clinically as a deep-seated mass associated with pain or tenderness. Severe functional disability at the time of presentation is associated with poorly differentiated, large tumors of long duration.[1]

Up to 50% of synovial sarcomas recur, usually within 2 years, but sometimes up to 30 years after initial diagnosis. Five year survival is 36 to 76%, and ten year survival is 20 to 63% with the best outcomes occurring in childhood patients.[5]

Radiographically, synovial sarcomas appear on x-ray as round or oval, more or less lobulated swellings of moderate density, usually located in close proximity to a large joint. The most striking feature, found in 15-20% of synovial sarcomas, is the presence of multiple small, spotty radiopacities caused by focal calcification and, less frequently, bone formation.[6]

The gross appearance varies depending on the rate of growth and the location of the tumor. The slow growing tumors tend to be well-circumscribed, round, or multilobular. As a result of compression of adjacent tissues by the expansively growing tumor, they are completely or partially invested by a smooth, glistening pseudocapsule. Cyst formation may be prominent, and occasional lesions present as multicystic masses.[7] Most tumors are firmly attached to surrounding tendons or tendon sheaths. They are usually tan-white and range in size from 3-15 cm with most tumors measuring falling into the 3-5 cm range. The more poorly differentiated tumors appear less well-circumscribed.[1,3,4] In our case the tumor had a tan-white, fleshy, and focally cystic cut surface. It was directly subjacent to the overlying tendon of the third metatarsal. The tumor surrounded, but did not appear to extend into the metatarsals. It expanded the surrounding muscle, but remained pseudoencapsulated with no adherence to any of the musculature.

Most synovial sarcomas fall into one of three categories being either monophasic, biphasic, or poorly differentiated. The classic synovial sarcoma is the biphasic subtype and is characterized by fascicles of spindle cells admixed with groups of epithelial cells that form clefts, cysts, cords, nests, tubules, or papillae. The epithelial cells are cuboidal to columnar with ovoid nuclei and a moderate amount of cytoplasm. The epithelial structures frequently contain intraluminal eosinophilic secretions.The spindle cell component consists mostly of plump, spindle-shaped cells of uniform appearance with small amounts of indistinct cytoplasm and oval dark-staining nuclei. The spindle cell component can have a herringbone pattern and appear almost identical to a fibrosarcoma. Numerous mast cells are frequently identified within the spindle cell component. Focal areas of myxoid, chondroid or osseous change can be seen.[1,3,4]

The monophasic subtype can be predominated by either the spindle cell component (more common) or the epithelioid component. In the former, the tumor is composed of fascicles of spindle cells, often with herringbone or hemangiopericytoid growth patterns. The epithelial component is inconspicuous. At low power, a pattern of alternating loose and dense areas is seen. Calcification, myxoid change, hyalinization, and mast cell infiltration may be present. Mitotic figures can be identified, but are not numerous.[1,3]

The poorly differentiated variant can be thought of as a form of tumor progression that can be superimposed on any of the other synovial sarcoma subtypes. The tumor can have three different patterns: a large-cell epithelioid pattern composed of variably sized, rounded nuclei with prominent nucleoli, a small-cell pattern, and a high grade spindle-cell pattern composed of spindle-shaped cells with high grade nuclear features and a high mitotic rate. The tumors can also have intracytoplasmic hyaline inclusions imparting a rhabdoid morphology. A hemangiopericytoma-like growth pattern is common, and it is thought that tumors previously interpreted as malignant hemangioperictyomas are in fact poorly differentiated synovial sarcomas.[1,3]

Immunohistochemically, synovial sarcomas display focal reactivity for cytokeratins and EMA, especially in the epithelioid component. The tumors also show cytoplasmic reactivity for CD99 and bcl-2 in both the epithelial and spindle cell components. The tumors are uniformly negative for CD34. Synovial sarcomas consistently show the t(X;18)(p11;q11) molecular alteration in up to 90% of cases leading to the SYT-SSX1/SSX2/SSX4 fusion genes.[1,3,4] The type of fusion protein formed affects the tumor morphology as well as the prognosis. Tumors with the SYT-SSX2 fusion gene showed an absence of glandular differentiation (monophasic), while those with SYT-SSX1 fusion gene were almost always the biphasic subtype. Moreover, those with the SYT-SSX2 mutation had a significantly higher five year survival rate than those with the SYT-SSX1 mutation. The SYT-SSX fusion type was determined to be the single most important prognostic factor in terms of overall survival.8 More recently, gene expression profiling studies have identified TLE1 as a potentially useful marker. In one series 91 out of 94 molecularly confirmed synovial sarcomas expressed TLE1 and in another series 35 out of 35 synovial sarcomas expressed the protein.[9,10] TLE1 was only rarely expressed by other tumors of mesenchymal origin. The authors of these case series concluded that TLE1 was more sensitive and specific than any other immnohistochemical marker available for synovial sarcoma.[9,10]

Bibliography

  1. Goldblum, John R., Andrew L. Folpe, Sharon W. Weiss, Franz M. Enzinger, and Sharon W. Weiss. Enzinger and Weiss's Soft Tissue Tumors. 6th ed. Philadelphia, PA: Elsevier Saunders, 2014. Print.
  2. Kumar, Vinay, Abul K. Abbas, and Jon C. Aster. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia, PA: Elsevier/Saunders, 2014. Print
  3. Gattuso, Paolo. Differential Diagnosis in Surgical Pathology. 2nd ed. Philadelphia, PA: Saunders/Elsevier, 2010. Print.
  4. Rosai, Juan, Lauren Vedder Ackerman, and Juan Rosai. Rosai and Ackerman's Surgical Pathology. 10th ed. Edinburgh: Mosby, 2011. Print.
  5. Fletcher, Christopher D. M. WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. Lyon: IARC, 2013. Print.
  6. Winnepenninckx, V., R. De Vos, M. Debiec-Rychter, I. Samson, P. Brys, A. Hagemeijer, and R. Sciot. "Calcifying/ossifying Synovial Sarcoma Shows T(X;18) with SSX2 Involvement and Mitochondrial Calcifications."Histopathology 38.2 (2001): 141-45.
  7. Morrison, Carl, Paul E. Wakely, Carol J. Ashman, Douglas Lemley, and Karl Theil. "Cystic Synovial Sarcoma." Annals of Diagnostic Pathology 5.1 (2001): 48-56.
  8. Ladanyi M, Antonescu CR, Leung DH, et al. (2002). "Impact of SS18-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients". Cancer Res. 62 (1): 135–40.