The recognition and characterization of soft tissue tumors is central to the practice of podiatric medicine. In many instances, clinicians of the lower extremity serve as the frontline physicians when it comes to the identification of such tumors. Given the inverse relationship between the amount of time prior to diagnosis and patient survival rates, the role of podiatrists may be of paramount importance. Depending upon one’s depth of experience and comfort level, some clinicians might limit their role to clinical recognition and ordering preliminary imaging studies. Others may go a step further and definitively characterize the lesion in question through needle aspiration, Tru-Cut core needle biopsy or incisional biopsy. In some instances, it is the podiatric surgeon who will provide definitive surgical management. The medical community at large is increasingly relying on the podiatric profession to recognize and raise awareness of skin, bone and soft tissue tumors of the lower extremity. Unfortunately, when podiatrists fail to diagnose these conditions, the resultant void may have grave consequences. Understanding And Defining Soft Tissue Tumors And Neoplasms The “soft tissue” is composed of all living tissue with the exception of that which is skeletal, epithelial, hematopoietic (bone marrow derived) and parenchymal (the functioning tissue of visceral organs). The nervous system is divided in such a way that the nerves and glia of the central nervous system are not considered part of the soft tissue but the nerves and nerves sheath of the peripheral nervous system are considered part of the soft tissue. In general terms, the soft tissues consist of adipose tissue, fibrous tissue, muscle, vascular structures and peripheral nerves. Accordingly, a pyogenic granuloma (composed of vessels) is a soft tissue tumor while squamous cell carcinomas and verrucae are not. Precisely what falls under the designation “soft tissue” does become a bit more complicated as some neoplasms of disputed differentiation are also under the classification of “soft tissue.” Some examples of this are synovial sarcoma and epithelioid sarcoma. Tumors of the soft tissue include all mass-forming lesions that are either composed of soft tissue or exhibit differentiation toward any type of soft tissue. It is important to note that although the central nervous system, visceral organs and skeletal system are not considered to be part of the soft tissue, they all have soft tissue within them in the form of vascular structures, adipose tissue, fibrous tissue and/or peripheral nerves. It is probably for this reason that we occasionally see tumors of the fibrous tissue (fibromatosis/pleomorphic fibroma, fibrosarcoma), adipose tissue (lipoma, liposarcoma) and smooth muscle (leiomyoma, leiomyosarcoma) arising in these unusual locations. Each type of soft tissue tumor has its own distinct pattern of distribution. Overall, however, the most common locations for soft tissue neoplasms are the retroperitoneum/pelvis and thigh. For clinicians who specialize in the care of the lower extremity, notable exceptions exist. Examples of soft tissue tumors that have a predilection for the distal extremities are synovial sarcoma, epithelioid sarcoma and clear cell sarcoma (melanoma of soft parts). One additional point that is highly relevant to the topic of soft tissue tumors involves the meaning of the term neoplasm. While soft tissue tumor refers to any mass occupying lesion that is composed of soft tissue elements, soft tissue neoplasm denotes only those tumors that emanate from a single genetically identical mother cell and proliferate as autogenous new growths (e.g., neoplasms). In other words, neoplasms begin with a genetic mutation or a series of genetic mutations within an individual mother cell, which results in immortality and the ability for that cell to replicate beyond normal physiologic limitations. This uncontrolled duplication of the mother cell ultimately leads to the formation of a mass. Neoplasms may be further subdivided into those that are benign and those that are malignant. A ganglion cyst is an example of a non-neoplastic soft tissue tumor, a lipoma is a benign neoplasm, a synovial sarcoma is a malignant neoplasm, etc. Unfortunately, the precise characterization of soft tissue neoplasms as benign or malignant may also be controversial. For example, Kaposi’s sarcoma, a vascular tumor induced by human herpes virus 8, was originally classified as a sarcoma. More recently, some investigators have argued that this lesion would be much better characterized as a virally induced hyperplasia because it may have features (multicentricity and spontaneous involution) that are not typical of neoplasia. Interestingly, tumors such as nodular fasciitis, tenosynovial giant cell tumor, superficial fibromatosis and dermatofibroma were all once uniformly believed to be non-neoplastic. However, based on genetic studies, some researchers now argue that these lesions are bona-fide neoplasms. Differentiating Soft Tissue Tumors: What You Should Know Many of the more clinically significant soft tissue tumors that arise in the distal lower extremities do so in the subcutis or deep soft tissue. This creates several problems for the treating clinician. These tumors may have a vague and nondescript clinical appearance as well as a tendency to remain cloaked by the surrounding tissues for an extended period of time prior to discovery. It is the deep location of these tumors that can make it very challenging, even for the experienced clinician, to deciphering their clinical significance. Features such as color, texture and the association with surrounding structures may be impossible to appreciate clinically. This may leave the lesion’s size as the preeminent clinical feature one uses to distinguish between lesions that are most likely benign and those that have a significant chance of being malignant. The conventional thinking is that soft tissue tumors have a formidable chance of being malignant when they are 5 cm in diameter. However, this measurement has serious limitations when one tries to apply it to soft tissue tumors of the distal extremity. Kirby, et. al., found that, unlike more proximal sites, size had little significance in distinguishing between benign and malignant soft tissue tumors in the foot.1 Unfortunately, once soft tissue sarcomas of the distal extremity have reached 5 cm in size, the patient’s prognosis has been significantly diminished.2 Moreover, unlike tumors of the deep soft tissue of the thigh or retroperitoneum, soft tissue tumors of the foot and ankle are usually discovered at a relatively early stage, whether it is the result of pain secondary to compression or due to the formation of an easily identified cutaneous mass. Simply waiting until such tumors become 5 cm in size prior to acting upon them would essentially surrender any prognostic benefit that might be had with a more timely diagnosis and initiation of treatment. The fact that small and intermediate-sized soft tissue tumors may be clinically indistinguishable from benign neoplasms and non-neoplastic lesions may have a profound impact on patient prognosis. The series by Scully, et. al., from Duke’s Department of Orthopedic Oncology, noted that delays of up to 21 months prior to the diagnosis of synovial sarcoma of the foot were introduced by the tendency of clinicians to manage patients with the working diagnosis of “ganglion” for extended periods without further investigation.3 This was also a point raised at Memorial Sloan Kettering when researchers reviewed a series of 401 soft tissue neoplasms of the foot.4 The history of trauma is a common red herring that may contribute to such delays. The series by Scully found that in 10 of 12 cases of pedal synovial sarcoma, the affected patient gave a history of trauma. Kirby, et. al., also found the history of trauma to be common and potentially misleading.1 Of course, there are some tumors that usually have a characteristic clinical appearance, namely, tumors of vascular differentiation. However, even these tumors, when high in grade (poorly differentiated), may not exhibit gross features that convey their line of differentiation. When it comes to tumors that arise more superficially, particularly those that are seated within the dermis, clinicians are not only more likely to identify these tumors as masses, they often may identify them accurately secondary to specific clinical features. For example, one may diagnose dermatofibromas clinically based on their dermal location, associated epidermal pigmentation and the presence of “Fitzpatrick’s sign” (dimpling with lateral pressure) and neurofibroma secondary to the characteristic flesh-like color and invagination under direct pressure (“buttonhole sign”). Neoplasms, such as synovial sarcoma, clear cell sarcoma, fibrosarcoma and sarcomas of smooth and skeletal muscle, typically lack such distinguishing features. Assessing The Incidence Of Common Soft Tissue Tumors Virtually any soft tissue tumor that has been described elsewhere in the human body may also arise in the distal lower extremities.4 When investigators have included both neoplasms and non-neoplastic tumors in large series on the subject, those tumors that are non-neoplastic consistently outnumber the former.1,5 Of course, as podiatric physicians are well aware, influencing such series are ganglion cysts which one sees with regularity in the soft tissue of the dorsal midfoot. In this location, ganglia may account for almost half of all soft tissue tumors.1 This is probably why some clinicians fall into the trap of assuming that all dorsal midfoot masses are ganglia, forgetting that this is also one of the most common locations for synovial sarcoma and it also may harbor numerous other high-grade sarcomas.1,4 As I already alluded to, the most common soft tissue tumors to arise in the foot are ganglion cysts.1 The next most common lesions are probably fibromatosis, followed by giant cell tumor of tendon sheath and lipoma.1,4 In my experience, if soft tissue proliferations of the skin were included in series on the subject, dermatofibroma would also be among the most common lesions identified. Among malignant soft tissue neoplasms, the most frequently occurring are synovial sarcoma, clear cell sarcoma and fibrosarcoma.4 When Kaposi’s sarcoma is classified as a malignant soft tissue tumor, it is overwhelmingly the most common such lesion identified in the foot.4 It is important to note that some relatively rare soft tissue sarcomas, such as epithelioid sarcoma and clear cell sarcoma, are actually overrepresented in the distal extremities.4 A Pertinent Primer On Biopsy Techniques The principal biopsy techniques clinicians use to characterize soft tissue tumors are needle aspiration biopsy, Tru-Cut core needle biopsy, incisional biopsy and excisional biopsy. These procedures are listed with regard to their degree of invasiveness, beginning with needle aspiration biopsy, which is minimally invasive, and ending with excisional biopsy, which is maximally invasive. Needle aspiration biopsy. Out of the listed techniques, needle aspiration biopsy is possibly the most useful for physicians of the lower extremity. Though it is the least invasive technique and the easiest to perform, it is also the least specific, commonly yielding diagnoses such as benign, suspicious or malignant. Even with its diagnostic limitations, needle aspiration biopsy may function as an excellent tool to alert clinicians to the possibility that a mass might require additional attention in the form of imaging, open biopsy or definitive surgery. When faced with the large number of mistreated sarcomas that had been followed for extended periods of time with the diagnosis of “ganglion,” Chou and Malawer concluded that clinicians should perform an aspiration biopsy on all ganglia and for those that did not yield sufficient tissue, one should take an open biopsy.6 One may perform this technique using a large gauge needle and a 5-cc syringe. Introduce the needle into the mass and then create a vacuum by pulling back on the piston/plunger. Without removing the needle from the tissue, partially withdraw it and then redirect it back into the tissue at various angles. Repeat this several times. Maintaining the vacuum, one should then remove the needle from the tissue. Clinicians who have experience in making slide preparations may use a portion of the aspirate to make a smear preparation. However, doing so is not typically mandatory. It is often acceptable to introduce the aspirate into formalin fixative (yet if one suspects tophaceous gout, alcohol is required). Draw the preservative into the syringe and reintroduce the fluid into the fixative jar, flushing the syringe of all potentially diagnostic cells. Tru-Cut core needle biopsy. When available, Tru-Cut core needle biopsy is possibly the best single biopsy technique for several reasons. This technique offers equal or higher sensitivity than incisional biopsy techniques with a significantly lower complication rate.7 Its relatively high sensitivity might be surprising in light of the fact that this technique provides substantially less tissue for histopathologic review than incisional techniques. This is probably the result of more representative sampling of the lesion in question. Researchers have also shown that the sensitivity of Tru-Cut core needle biopsy is higher than that of fine needle aspiration biopsy.8 One would perform Tru-Cut core biopsies with a biopsy device that is reminiscent of what is used to obtain bone marrow core biopsies. Using this technique, the clinician should obtain one or more cores of tissue measuring roughly 1.5 mm in diameter from the lesion in question. One may then redirect the biopsy instrument multiple times through the same skin incision to sample multiple regions within the tumor. After collecting the tissue samples, place them in formalin fixative. Incisional biopsy. Incisional biopsy involves obtaining a small part of a larger lesion. In this context, it is often equated with “open biopsy” in that one incises the skin and removes a wedge of tumor for histopathologic examination. When there is a high index of suspicion for malignancy, podiatric physicians should refer to clinicians who will offer definitive care as it may complicate the definitive surgery for high-grade sarcomas. Excisional biopsy. This technique involves the complete removal of the lesion in question. This procedure should also be the domain for clinicians who will provide definitive care when there is a high index of suspicion for malignancy. Insufficient excisions may lead to indeterminate margins, which may subsequently result in an otherwise unnecessary amputation. The indications for biopsy of soft tissue tumors are not clear-cut and have never been adequately defined. Criteria such as size (5 cm) have little role in the foot. However, other findings that should prompt a biopsy include long duration of an unexplained mass (> four weeks), rapid growth and spontaneous ulceration. As a general rule, clinicians should investigate all unexplained masses and those discrete masses that are erroneously attributed to trauma. Clinicians can more readily sample skin-based masses by employing the shave technique, punch technique or excisional technique. One may initially biopsy more deeply seated lesions using needle aspiration technique and possibly follow this by obtaining imaging studies (MRI). When the cytopathologic findings or imaging studies warrant continued or increased suspicion, one may perform a Tru-Cut core needle biopsy or refer the patient to an alternate center for definitive treatment. It is important to restate that all malignancies first begin as small tumors. It is ill advised to wait for extended periods of time prior to investigating such tumors based on the lack of sufficient size. Final Thoughts Clinicians must confront a genuine dilemma when dealing with patients with soft tissue tumors. That dilemma concerns the fear of somehow damaging the integrity of the surgical site by investigating a soft tissue tumor versus doing nothing and therefore doing harm to the patient by not making the diagnosis of sarcoma in a timely fashion. Needle aspiration biopsy, possibly with imaging studies, may be a way to characterize a soft tissue tumor while minimizing potential biopsy-related complications. When such studies do not favor the diagnosis of malignancy, podiatric surgeons may feel more comfortable managing the patient’s condition. Tru-Cut core needle biopsies are excellent procedures for those physicians with experience using this technique. Dr. Bakotic is the Director of the Institute for Podiatric Pathology in Pompano Beach, Fla. He is also a Diplomate of the American Board of Pathology. References 1. Kirby EJ, Shereff MJ, Lewis MM. Soft tissue tumors and tumor-like lesions of the foot. An analysis of eighty three cases. J Bone Joint Surg [Am] 71-A:621-626, 1989. 2. Hajdu SI, Shiu MH, Foutner JG. Tenosynovial sarcoma: A clinicopathological study of 136 cases. Cancer 39:1201-1217, 1977. 3. Scully SP, Temple HT, Harrelson JM. Synovial sarcoma of the foot and ankle. Clin Orthop Rel Res 364:220-226, 1999. 4. Bakotic BW, Borkowski P. Primary soft-tissue neoplasms of the foot: The clinicopathologic features of 401 cases. J Foot Ankle Surg 40:28-35, 2001. 5. Ozdemir HM, Yildiz Y, Yilmaz C, Saglik Y. Tumors of the foot and ankle: Analysis of 196 cases. J Foot Ankle Surg 36:403-408, 1997. 6. Chou LB, Malawer MM. Analysis of surgical treatment of 33 foot and ankle tumors. Foot and Ankle Intl 15(4):175-181, 1994. 7. Hoeber I, Spillane AJ, Fisher C, Thomas JM. Accuracy of biopsy techniques for limb and limb girdle soft tissue tumors. Ann Surg Oncol 8(1): 80-87, 2001. 8. Yang YJ, Damron TA. Comparison of needle core biopsy and fine needle aspiration for diagnostic accuracy in musculoskeletal lesions. Arch Pathol Lab Med 128:759-764, 2004. For related articles, see “Diagnosing Malignant Bone Tumors In The Lower Extremity” in the August 2004 issue of Podiatry Today.
CE Exam#141 Choose the single best response to each question listed below: 1. Which of the following is a non-neoplastic soft tissue tumor? a) Ganglion cyst b) Synovial sarcoma c) Fibromatosis d) Epithelioid sarcoma 2. Recently, investigators have argued that Kaposi’s sarcoma should be classified as a … a) malignant neoplasm b) virally induced hyperplasia c) sarcoma d) benign neoplasm 3. Once soft tissue sarcomas of the distal extremity have reached ___ in size, the patient’s prognosis is significantly diminished. a) 1 cm b) 2 cm c) 4 cm d) 5 cm 4. What does Fitzpatrick’s sign include? a) Dimpling with lateral pressure b) Indistinct borders c) Invagination under direct pressure d) Poor vascular differentiation 5. What is one disadvantage of needle aspiration biopsy? a) It is a relatively invasive technique. b) It is the least specific technique as it commonly yields diagnoses such as benign, suspicious or malignant. c) It is difficult to perform. d) None of the above 6. The needle aspiration biopsy ... a) offers equal or higher sensitivity than incisional biopsy techniques with a significantly lower complication rate. b) offers greater sensitivity than a Tru-Cut core needle biopsy. c) is an excellent tool to alert clinicians to the possibility that a mass might require additional attention in the form of imaging, open biopsy or definitive surgery. d) all of the above 7. What are the most common soft tissue tumors to arise in the foot? a) Giant cell tumor of tendon sheath b) Lipoma c) Ganglion cysts d) Fibromatosis 8. The Tru-Cut core needle biopsy … a) offers less sensitivity than incisional biopsy techniques with a higher complication rate. b) has a higher sensitivity than that of fine needle aspiration biopsy. c) involves the complete removal of the lesion in question. d) none of the above 9. Which of the following findings should prompt a biopsy? a) Long duration of an unexplained mass (greater than four weeks) b) Rapid growth c) Spontaneous ulceration d) All of the above 10. When it comes to more deeply seated lesions, one may initially biopsy these with … a) the punch technique b) an excisional technique c) a needle aspiration technique d) none of the above Instructions for Submitting Exams Fill out the enclosed card that appears on the following page or fax the form to NACCME at (610) 560-0502. Within 60 days, you will be advised that you have passed or failed the exam. A score of 70 percent or above will comprise a passing grade. A certificate will be awarded to participants who successfully complete the exam. Responses will be accepted up to 12 months from the publication date.