How To Differentiate Soft Tissue Neoplasms

     Soft tissue neoplasms of the lower extremity present a significant treatment challenge to the treating physician. Although most neoplasms of the lower extremity prove to be benign, the potential for malignancy does exist. The ability to appropriately diagnose and treat soft tissue neoplasms may be the difference between life and death for the patient presenting with a soft tissue tumor of the lower extremity.      Accordingly, let us take a closer look at appropriate evaluation and diagnostic techniques that will aid the physician in making an accurate diagnosis when he or she is presented with a soft tissue neoplasm of the lower extremity.      The soft tissue is defined as nonepithelial, extraskeletal tissue exclusive of the lymphohematopoietic tissue. It includes fibrous connective tissue, adipose tissue, skeletal muscle, blood and lymph vessels, and the peripheral nervous system. Any of these tissues may be the histologic source of a soft tissue neoplasm.      Tumors have traditionally been defined according to their histogenic features. New data suggests that most sarcomas arise from primitive, multipotential mesenchymal cells, which, in the course of neoplastic transformation, differentiate into one or more tissue lines. Clinically, tumors are classified based on location, growth pattern and likelihood of recurrence, the presence and location of metastases, the patient’s age and overall prognosis. Tumors are generally classified as benign or malignant. It is important to understand that many soft tissue tumors are of an intermediate nature. This implies aggressive local behavior and a low to moderate potential to metastasize.      The true incidence of soft tissue neoplasms of the lower extremity is impossible to quantify. Many soft tissue tumors are unreported due to their predominately benign behavior. One study found that benign tumors outnumbered malignant neoplasms by a ratio of 100:1.1 Primary sarcomas presenting below the knee comprise approximately 8 percent of the nearly 5,000 sarcomas diagnosed each year.      The most common benign tumors are ganglion cysts and plantar fibromas. Synovial sarcomas represent the most common malignant tumor isolated and have a predilection for the lower extremities.2 One must also consider soft tissue tumors of metastatic origin when evaluating the patient with a soft tissue mass. Although rare, there are cases of metatastatic soft tissue neoplasms without osseous involvement.3      There are a number of factors that may influence the development of a soft tissue neoplasm. Hereditary or genetic factors, exposure to chemicals or ionizing radiation, infection, trauma, chronic lymphedema, metastasis and local recurrence of a previous neoplasm have all been implicated in the development of soft tissue tumors.

Keys To The Initial Evaluation Of A Patient With A Soft Tissue Mass

     The initial evaluation should include a thorough history. One should consider all soft tissue masses of the extremities to be a primary sarcoma until proven to the contrary. The physician’s history should review the patient’s complaints regarding the mass and its effect on the patient. Questioning regarding the onset, growth rate and symptoms associated with the mass will allow the physician to understand which anatomic structures are potentially involved. The social and past medical histories may identify risk factors for tumor growth.      The presence of known etiologic factors that influence tumor growth is an important finding in the patient history. A complete review of systems will provide information as to whether other disease states are contributory to the development of the lower extremity soft tissue neoplasm.      Physical examination of the soft tissue tumor and the extremity is the next logical phase of the evaluation. One should perform a complete dermatologic, vascular, neurologic and musculoskeletal exam. The exam should not be limited to the anatomic region of the mass. Undertake a complete exam of the patient to ensure the mass is truly solitary. It is particularly important in the lower extremity to evaluate the lymphatic system and the presence or absence of palpable lymph nodes.      The location, size, consistency, mobility, effect on surrounding anatomic structures and the presence of pain are important physical exam findings.4 Tumors that are large, firm and indistinct generally raise more concern than small, geometric tumors that are cystic, mobile and in the subcutaneous layer.4,5 Pain at the site of the tumor can be generated from the mass itself or from impingement on adjacent anatomic structures. Understanding the effect that the mass has on the extremity gives the physician clues to the structures that may have undergone neoplastic change or those that are affected by such change.

What You Should Know About Laboratory And Imaging Studies

     There are no specific laboratory tests for the diagnosis of soft tissue tumors. One should use laboratory testing in the evaluation of patients with soft tissue neoplasms as part of the general workup for systemic conditions identified in the history and physical.      Obtain imaging studies to assist with the staging of soft tissue neoplasms. Radiographs, computed tomography (CT) and magnetic resonance imaging (MRI) are frequently used in the evaluation of soft tissue neoplasms. Obtain all imaging studies prior to biopsy of the soft tissue tumor.6 Obtaining studies after the biopsy is less useful due to an inability to determine the local extent of the tumor.6,7 Physicians commonly order CT scans to evaluate the lungs for metastases. Magnetic resonance imaging is particularly useful in determining the relationship of the tumor and the normal surrounding soft tissue envelope. This assists the surgeon in accurate pre-biopsy planning and further illustrates the importance of appropriate imaging prior to biopsy or surgery.

Pertinent Insights On The WHO Classification Of Soft Tissue Tumors

     The World Health Organization (WHO) has developed a classification scheme to delineate soft tissue tumors. The classification describes the tumors based on histologic characteristics and subdivides the tumors into benign or malignant categories.      Adipocytic tumors. Benign tumors include lipoma, lipomatosis, lipomatosis of nerves, lipoblastoma, angilipoma, myolipoma, chondroid lipoma, extrarenal angiolipoma, extra-adrenal myelolipoma, spindle-cell/pleomorphic lipoma and hibernoma.      Intermediate tumors include atypical lipomatous tumor and well differentiated liposarcoma.      Malignant tumors include dedifferentiated liposarcoma, myxoid liposarcoma and round cell liposarcoma. The tumors also include pleomorphic liposarcoma, mixed-type liposarcoma and liposarcoma (not otherwise specified).      Fibroblastic/myofibroblastic tumors. Benign tumors include nodular fasciitis, proliferative fasciitis, proliferative myositis, myositis ossificans, ischemic fasciitis, elastofibroma, fibrous hamartoma of infancy, myofibroma/myofibromatosis, fibromatosis colli, juvenile hyaline fibromatosis, inclusion body fibromatosis, fibroma of tendon sheath, desmoplastic fibroblastoma, mammary-type myofibroblastoma, calcifying aponeurotic fibroma, angiofibroblastoma, cellular angiofibroma, nuchal-type fibroma, Gardner fibroma, calcifying fibrous tumor and giant cell angiofibroma.      Intermediate (locally aggressive) tumors include superficial fibromatosis – palmar/plantar, desmoid-type fibromatoses and lipofibromatosis.      Intermediate (rarely metastasizing) tumors include solitary fibrous tumor and hemangiopericytoma and inflammatory myofibroblastic tumor. These tumors also include low-grade myofibroblastic sarcoma, myxoinflammatory fibroblastic sarcoma and infantile fibrosarcoma.      Malignant tumors include adult fibrosarcoma, myxofibrosarcoma, low-grade fibromyxoid sarcoma and sclerosing epithelioid fibrosarcoma.      Fibrohistiocytic tumors. Benign tumors include giant cell tumor of tendon sheath, diffuse-type giant cell tumor and deep benign fibrous histiocytoma.      Intermediate tumors include plexiform fibrohistiocytic tumor and giant cell tumor of soft tissues.      Malignant tumors include pleomorphic MFH/undifferentiated pleomorphic sarcoma, giant cell MFH/undifferentiated pleomorphic sarcoma with giant cells and inflammatory MFH/undifferentiated pleomorphic sarcoma with prominent inflammation.      Smooth muscle tumors. Benign tumors include angioleiomyoma, deep leiomyoma and genital leiomyoma.      Malignant tumors include leiomyosarcoma excluding skin.      Pericytic tumors. These types are glomus tumor and malignant glomus tumor as well as myopericytoma.      Skeletal muscle tumors. A benign tumor is rhabdomyoma.      Malignant tumors include embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma and pleomorphic rhabdomyosarcoma.      Vascular tumors. Benign tumors include hemangiomas of subcutaneous and deep soft tissue, epithelioid hemangioma, angiomatosis and lymphangioma.      Intermediate (locally aggressive) tumors include kaposiform hemangioendothelioma.      Intermediate (rarely metastasizing) tumors include retiform hemangioendothelioma, papillary intralymphatic angioendothelioma, composite hengioendothelioma and Kaposi sarcoma.      Malignant tumors include epithelioid hemangioendothelioma and angiosarcoma of soft tissue.      Chondro-osseous tumors. A benign tumor is soft tissue chondroma.      Malignant tumors include mesenchymal chondrosarcoma and extraskeletal osteosarcoma.      Tumors of uncertain differentiation. Benign tumors include intramuscular myxoma, juxta-articular myxoma, deep angiomyxoma, pleomorphic hyalinizing angiectatic tumor and ectopic hamartomatous thymoma.      Intermediate (rarely metastasizing) tumors include angiomatoid fibrous histiocytoma, ossifying fibromyxoid tumor and mixed tumor.      Malignant tumors include synovial sarcoma and epithelioid sarcoma. Also included are alveolar soft-part sarcoma, clear cell sarcoma of soft tissue, extraskeletal myxoid chondrosarcoma, primitive neuroectodermal tumor/extraskeletal Ewing tumor, desmoplastic small round cell tumor, extrarenal rhabdoid tumor, malignant mesenchymoma, neoplasms with perivascular epithelioid cell differentiation and intimal sarcoma.

How To Stage Soft Tissue Neoplasms

     One would perform the staging of benign and malignant soft tissue neoplasms to determine the extent of the disease at the time of diagnosis. Physicians should take the histologic grade, size, site, lymph node involvement and the presence of metastasis by the different staging systems into consideration.      In regard to the different staging systems, see “A Guide To The American Joint Committee Staging Protocol For Soft Tissue Sarcomas” on page 44, “How The Enneking System Stages Soft Tissue Sarcomas And Sarcomas Of Bone” above and “A Guide To The Enneking System For Staging Benign Soft Tissue Masses” above.7,8

Pertinent Pointers On Taking Biopsies

          The biopsy is a critical component in the workup of a soft tissue neoplasm. One should complete the pre-biopsy evaluation of the patient and use any necessary advanced imaging modalities to further assess the tumor before taking the biopsy. Studies such as MRI, CT or ultrasound will be of less diagnostic value if the physician obtains them after the biopsy.      Meticulous planning of the biopsy will ensure retrieval of an adequate specimen for histologic grading. This will facilitate accurate staging of the lesion and assist in guiding definitive care for the patient. The placement of all biopsies, whether closed or open, has a significant impact on the final outcome for the patient. A poorly performed biopsy may result in transverse incisions that violate lymphatic channels, the development of hematoma formation, tumor spread and inadequate specimen retrieval. This often may be the difference in successful treatment via reconstructive efforts versus proximal amputation of the extremity.      Preferably, the surgeon who will treat the neoplasm definitively will be the one to perform the biopsy. When one has a high index of suspicion for malignancy during the pre-biopsy evaluation of a neoplasm, appropriate referral to a surgeon experienced in treating these conditions is recommended.9      The placement of the biopsy is crucial. One should place biopsies in a manner that limits the potential for tumor spread and allows complete excision of the biopsy tract when performing the definitive procedure. When determining the biopsy placement, the physician must have a thorough understanding of the reconstructive efforts that one may employ to salvage the limb.      Perform closed biopsies percutaneously to obtain a small tissue sample. When it comes to fine needle aspiration, one would typically utilize a 25-gauge needle and syringe to obtain a specimen of the neoplasm. The physician would perform a core-needle biopsy in a similar manner. They generally consist of a cannulated needle and trochar that allows for collection. The advantage of these techniques includes the decreased risk of hematoma formation and potential tumor spread. The main disadvantage is the potential for not obtaining enough specimen for analysis or obtaining specimen that is not representative of the entire tumor.9      Open biopsies imply that the surgeon uses an incision to obtain the specimen. Excisional biopsies remove the mass completely. Physicians often employ excisional biopsies for neoplasms less than 2 cm or those thought to be of a benign nature. One may also utilize the excisional biopsy for superficial masses that do not extend past the deep fascia. Consider large and deeper masses malignant until proven otherwise.      Incisional biopsies are the most commonly employed open technique for soft tissue masses that have the potential for malignancy. The main advantages of this technique are the ability to obtain an adequate tissue specimen and avoid less local tumor spillage as opposed to an excisional biopsy. When performing open biopsies, the surgeon should strongly consider obtaining appropriate intraoperative cultures to rule out infection as a source of tumor development.9

Case Study: When A Slow Growing Mass Suddenly Causes Adjacent Toe Pain

     A 30-year-old male presented to clinic with a complaint of a slowly growing mass of the right fifth toe since childhood. The mass recently began to cause adjacent toe pain and the patient requested removal of the mass for this reason. The patient’s past medical history was unremarkable and his exam was notable for a large mass to the distal right fifth toe with subtle duplication of the distal phalanx. The patient underwent excision of the mass with a concomitant distal Syme’s amputation of the toe.      The histologic analysis identified the mass as a benign collagenoma. The patient was referred to endocrinology due to a high association of collagenomas with multiple endocrine neoplasia type -1 (MEN1).10 Additional workup determined this was a solitary tumor without evidence of MEN1. The patient recovered from the procedure without incident and has had no recurrence of his neoplasm.

In Conclusion

     Soft tissue neoplasms of the lower extremity present a significant diagnostic and therapeutic challenge. Accurate identification of the soft tissue tumor coupled with a well thought out treatment plan will result in the best outcome for the patient. All physicians need to be well versed in the appropriate way to initially evaluate a soft tissue neoplasm. A high index of suspicion for malignancy will avoid the initiation of a treatment that may have a deleterious effect for the patient. Referral to physicians who specialize in the care of malignant neoplasms is appropriate if there is a high index of suspicion for malignancy during the initial evaluation of the patient. Dr. Rottier is an Assistant Professor of Podiatric Surgery in the Department of Orthopaedic Surgery and Rehabilitation at Loyola University Medical Center in Maywood, Ill. He is a Fellow of the American College of Foot and Ankle Surgeons.
 

References:

1. Albus-Lutter LE, de Stefani E, van Unnik JM. Clinicopathologic relationship in soft tissue sarcoma. In: Albus-Lutter, de Stefani E, van Unnik JM eds. Management of soft-tissue sarcomas. New York: Raven, 1986:27-34.

2. Kirby EJ, Shereff MJ, Lewis MM. Soft tissue tumors and tumor-like lesions of the foot: analysis of eighty-three cases. J Bone Joint Surg Am 1989;71:621-626.

3. Hattrup SJ, Amadio PC, Sim FH, et al. Metatstaic tumors of the foot and ankle. Foot Ankle 1988;8:243-247.

4. Enneking WF. Musculoskeletal tumor surgery, vols 1 and 2. New York: Churchill Livingstone, 1983:1-38, 4647-4713.

5. Shiu MN, Brennan MF. Surgical management of soft tissue sarcomas. Philadelphia: Lea and Febiger, 1989:45-124.

6. Fletcher CD. The evolving classification of soft tissue tumors: an update based on the new WHO classification. Histopathology 2006 Jan; 48(1)3-12.

7. American Joint Committee on Cancer. Soft Tissues. In: Beahrs OH, Myers MH eds, Manual for staging of cancer. 3rd ed. Philadelphia: JB Lipincott; 1988:127.

8. Enneking WF. Staging of musculoskeletal tumors In: Enneking WF, ed. Musculoskeletal tumor surgery. New York: Churchill Livingstone;1983:87.

9. Simon MA, Springfield D. Chapter 6 Biopsy In: Simon MA, Springfield D eds. Surgery for Bone and Soft Tissue Tumors. 1998 Lippincott-Raven.

10. Xia Y, Darling TN rapidly growing collagenomas in multiple endocrine neoplasia type 1. J Am Acad Derm, 2007 May;56(5):877-80. Additional Reference 11. Simon MA, Springfield D. eds. Surgery for Bone and Soft Tissue Tumors. 1998 Lippincott-Raven.