College of American Pathologists
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The Role of Cytogenetics in Soft Tissue Tumors

Posted December 1, 2006

Jean Thomsen, MD
CAP Cytogenetics Resource Committee

The majority of soft tissue tumors are benign and have a very high cure rate after surgical excision. Malignant mesenchymal neoplasms, i.e., soft tissue sarcomas, amount to less than 1% of malignant tumors.1 These can occur anywhere, but they are most frequently seen in the extremities, followed by the trunk wall and the retroperitoneum. Males are more commonly affected than females and the median age of occurrence is 65 years of age.1

Traditionally, soft tissue tumors were classified according to the architectural and cytologic features that resemble one of their normal counterparts such as cartilage, fat, muscle or nerve. However, the tumor cells can be so poorly differentiated that it is difficult, if not impossible, to categorize the cell of origin. Genetic analysis has been an indispensable aid for classifying these tumors where the morphological and immunohistochemical findings are equivocal.

Cytogenetic analysis of soft tissue tumors is used to detect and characterize chromosomal abnormalities for diagnosis, prognosis and patient care management. Cytogenetics may be used at the time of initial diagnosis as well as in subsequent resections to look for disease recurrence. Many soft tissue tumors contain clonal cytogenetic and molecular abnormalities that are diagnostic of a particular tumor type; a substantial number of these tumors are characterized by translocations (Table 1). In the pediatric population especially, it is imperative that cytogenetics be performed, as diagnosis and prognosis are closely tied to the cytogenetic abnormality. In the adult population, the use of cytogenetic analysis is recommended if diagnostic or prognostic information can be gleaned.

Classic cytogenetics requires fresh, viable tumor specimens that should be processed in a sterile fashion as rapidly as possible for transportation to the laboratory. When submitting tissue for conventional cytogenetics, it is helpful to provide a differential diagnosis so that the laboratory can choose the appropriate culture setup. The tumor cells are grown in the laboratory, after which they are harvested for chromosome analysis.2 This traditional type of analysis can demonstrate loss or gain of whole chromosomes, rearrangements affecting large regions of individual chromosomes and large deletions or amplifications.

Fluorescent in situ hybridization (FISH) can be used to map loci on specific chromosomes, detect chromosomal rearrangements, document numerical chromosomal abnormalities and reveal more subtle abnormalities, such as small deletions or point mutations.3 Also, FISH can be performed on fresh, frozen or paraffin-embedded material and generally has a more rapid turn-around time. The disadvantage is that one must have some idea of the suspected genetic abnormality prior to testing because it is not practical to probe for all defects.

The re-classification of soft tissue tumors that has occurred since the widespread use of cytogenetic testing has certainly increased diagnostic accuracy, provided important prognostic information and laid the groundwork for the advancement of gene therapy. However, it is not meant to be a replacement for histology. It is important for the surgeon, the surgical pathologist and the cytogeneticist to communicate among each other and develop an appropriate plan, so the patient has the best possible outcome.


  1. Fletcher C, Unni K, Mertens F. Soft tissue tumours: Epidemiology, clinical features, histopathological typing and grading. In: Tumours of Soft Tissue and Bone. Lyon, France: IARC Press. 2002:12–17.
  2. Sandberg A. Cytogenetics and molecular genetics of bone and soft-tissue tumors. American Journal of Medical Genetics. 2002;115:189–193.
  3. 3. Pfeifer J, Hill D, O’Sullivan J, Dehner L. Diagnostic gold standard for soft tissue tumours: morphology or molecular genetics? Histopathology. 2000;37:485–500.

Tumor Genetic Abnormality Reason for Testing
Alveolar rhabdomyosarcoma t(1;13)(q36;q14) Better outcome
Alveolar rhabdomyosarcoma t(2;13)(p35;q14) Poorer outcome
Alveolar soft part sarcoma t(X;17)(p11;q25) Diagnostic
Clear cell sarcoma t(12;22)(q13;q12) Distinguish from cutaneous melanoma
Desmoplastic small round cell tumor t(11;22)(p13;q12) Poor prognosis
Embryonal rhabdomyosarcoma Complex structural and numerical changes Corroborate histologic diagnosis
Ewing sarcoma/Peripheral neuroectodermal tumor (PNET) t(11;22)(q24;q12),
other less common variants
Distinguish from other small round cell tumors
Extraskeletal myxoid chondrosarcoma t(9;22)(q22;q12) Diagnostic
Infantile fibrosarcoma t(12;15)(p12;q26),
+8, +11, +17, +20
Distinguish from more aggressive adult fibrosarcoma
Myxoid liposarcoma t(12;16)(q13;p11) Diagnostic
Synovial sarcoma t(X;18)(p11;q11) Differentiate biphasic from monophasic

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NewsPath® Editor: Megan J. DiFurio, MD, FCAP
This newsletter is produced in cooperation with the College of American Pathologists Public Affairs Committee and may be reproduced in whole or in part as a service to the medical community. Copyright © 2006 by the College of American Pathologists.
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