Diagnosing soft tissue tumors requires a combination of clinical information and adequate, well-processed tissue. At a minimum, the pathologist should know the patient’s age, tumor location, and growth characteristics. In many cases, the results of imaging studies, particularly magnetic resonance imaging (MRI), enhance one’s understanding of the clinical extent of the tumor and its relationship to normal structures (see Chapter 3 ).

Although age rarely, if ever, suggests a particular diagnosis, it is important to know whether the patient is a child or an adult. In general, there is little overlap between soft tissue tumors occurring in children and those in adults. Therefore, this critical information presents the pathologist with two groups of tumors from which a differential diagnosis can be constructed. For example, undifferentiated pleomorphic sarcoma is essentially unheard of during childhood, so one should consider other diagnoses for a pleomorphic tumor in a child. On the other hand, neuroblastoma virtually never occurs after childhood, and such diagnoses should always be made cautiously in adults.

Location may also help narrow the differential diagnosis. For the most part, sarcomas develop as deeply located masses and infrequently present as superficial lesions. Exceptions do occur, however, and include lesions such as pleomorphic dermal sarcoma, dermatofibrosarcoma protuberans (DFSP), epithelioid sarcoma, Kaposi sarcoma, and angiosarcoma ( Box 5.1 ). It is also useful to remember that when carcinomas or melanomas metastasize to soft tissue, they do so usually as small, superficial nodules rather than as large, deeply situated masses. The most common carcinomas that present as soft tissue metastases are pulmonary and renal carcinomas, the former usually appearing as a subcutaneous mass on the chest wall and the latter as a soft tissue mass in almost any location.

Unfortunately, there is a significant overlap in the clinical presentation of benign and malignant soft tissue tumors, so this information may be unhelpful to the pathologist. Most soft tissue sarcomas of the extremities are detected by the patient as a slowly growing mass that has been present for 6 months or more at the time of diagnosis. The duration of benign lesions may be similar, although they are generally described as static or slowly growing. An exception is the rapid development of some cases of nodular fasciitis and related lesions. These superficial, pseudosarcomatous, benign tumors may develop rapidly over 1 to 3 weeks, and we have even encountered some that evolved in a few days, a pattern of growth that seldom, if ever, is encountered with a sarcoma. Therefore, an astute surgeon can sometimes suggest the diagnosis of nodular fasciitis for a rapidly evolving superficial lesion of the extremity. One should keep in mind, however, that not all patients are reliable historians.

In the past, the choice of biopsy technique for soft tissue masses was dictated by the size and location of the tumor (see Chapter 2 ). An incisional biopsy was considered the gold standard for large, deeply situated masses and provided ample material for diagnosis and ancillary studies. Its principal disadvantages included spillage of tumor into adjacent compartments as a result of poor hemostasis or faulty biopsy placement, complications of wound infection, and the usual requirement for hospitalization of the patient. Excisional biopsy, although more expedient and providing the entire lesion for examination, was performed on only small, superficial lesions amenable to complete resection. The current reliance on minimally invasive techniques to procure tissue has significantly changed the biopsy paradigm in the direction of core-needle biopsy (CNB). The use of CNB increased from less than 10% to almost 80% of tumors during the early 1990s and now is performed in our hospitals on essentially all deep soft tissue masses. Consequently, the amount of material available to type and grade sarcomas has significantly decreased, and this trend is likely to continue unabated because of the emphasis on less-costly outpatient care. Therefore, it is important to be aware of the limitations and pitfalls of CNB and to keep in mind a few basic principles. ^,

First, the pathologist should be aware of the clinician’s expectations. In some cases, the goal of a CNB may be simply to establish that a soft tissue mass is a mesenchymal neoplasm as opposed to a lymphoma or metastatic lesion. This distinction can usually be made in most cases either morphologically or with judicious use of immunohistochemistry. If definitive surgery will be performed following the needle biopsy, then the most important priority is to determine whether the lesion is a sarcoma. If, however, the intention is to provide preoperative (neoadjuvant) radiotherapy and/or chemotherapy, every attempt should be made not only to make the diagnosis of sarcoma but also to specifically classify and grade the tumor. However, as discussed in Chapter 1 , it is not always possible to grade a sarcoma reliably based on a CNB. Pathologists may find that the best assessment they can give is the designation low-grade or high-grade, recognizing that high-grade will encompass both grade 2 and 3 lesions. Information is inevitably lost when collapsing a three-tiered system into a two-tiered one; however, a two-tiered system still performs reasonably well and is consistent with therapeutic considerations.

In grading CNBs, one can usually accept the presence of high-grade areas in several needle cores as diagnostic of a high-grade sarcoma because of the improbability that additional material will result in downgrading the lesion. At the same time, one should also be unwilling to accept a lesion as a low-grade if the number of core biopsies is small, if the lesion has not been adequately sampled, or if imaging studies suggest features of a high-grade sarcoma (i.e., necrosis). CNBs containing necrosis usually imply a high-grade sarcoma, again because of the improbability that limited material captures a solitary or limited focus of necrosis. However, pathologists must be certain that necrosis is of the coagulative and not the hyaline type and is not reflective of prior therapy or surgical intervention. The corollary to the latter portion of this statement is that as soon as radiation or chemotherapy has been administered, grading becomes unreliable because of alterations in nuclear features, mitotic activity, cellularity, and interstitial hyalinization. Therapy also induces necrosis, although it is not possible to discriminate spontaneous from therapy-induced necrosis. Most importantly, interpreting CNBs necessitates a close dialog with clinicians and radiologists to resolve any inconsistencies between the clinical and pathologic diagnoses.

In the past, frozen section examinations were performed with the expectation that definitive surgery would be undertaken during the same intraoperative procedure, but this trend has changed. Frozen sections are now obtained primarily to assure the surgeon that representative, viable tissue has been obtained that is adequate for a permanent section diagnosis or to evaluate margins. The former may be accomplished by freezing a portion of the biopsy specimen or sometimes by performing a touch preparation. The presence of malignant cells in a nonnecrotic background on a touch preparation usually ensures that the specimen is adequate. A background of reactive or necrotic cells suggests that a biopsy sampled the pseudocapsule or that the specimen is largely necrotic, requiring additional material depending on the clinical impression.

Because the preference is to perform limb-sparing surgery for sarcomas of all types, if possible, the number of amputation specimens received in the surgical pathology laboratory has greatly decreased. Sarcomas of the extremities are ideally resected in an oncologic fashion, with a cuff of normal tissue; many will also receive preoperative or postoperative radiotherapy with or without chemotherapy. Optimally, such specimens are received fresh and unfixed so that tissue for ancillary studies can be obtained. As with many other surgical specimens, the margins should be marked with permanent ink and blotted dry before the dissection of the specimen. Whenever possible, the gross specimen should be evaluated with the surgeon in order to best appreciate the relationship of the mass to normal anatomic structures and the location of possible close margins. After the incision, the gross characteristics of the tumor should be noted. If malignancy is suspected, carefully assessing the tumor to its surroundings is mandatory. This includes the location of the lesion (e.g., subcutis, muscle), its size, its relation to vital structures (e.g., bone, neurovascular bundle), and the relative amount of necrosis if it can be judged grossly. Size is important for providing an accurate T descriptor for the surgeon if the lesion is a sarcoma. Assessing the degree of necrosis is important for untreated sarcomas because this parameter is part of the French (FNCLCC) grading system. The extent of necrosis in tumors treated with preoperative irradiation, chemotherapy, or a combination of both is important to note because it helps the clinician assess the efficacy of therapy. It is, however, unclear if the extent of tumor necrosis after preoperative treatment correlates with outcome. Some studies have shown the presence of posttreatment hyalinization/fibrosis to be an independent prognostic factor for overall survival. ^, It might, therefore, be indicated to document the amount of necrosis, the type of necrosis, and the presence of hyalinization/fibrosis in the pathology report. Often, the gross appearance of the tumor is deceptive. Sarcomas may appear circumscribed, and benign tumors occasionally infiltrate. The use of the term encapsulation can be misleading and can invite inadequate excision by shelling out or enucleating the tumor. In reality, sarcomas lack a true capsule and instead are surrounded by a compressed zone of normal tissue, known as a pseudocapsule .

There are no rigid guidelines for sampling soft tissue tumors; to some extent, sampling is dictated by the specific case. In the case of a known benign lesion, a few representative sections suffice (or the entire lesion if it is small). With a sarcoma, the questions to be answered are different. For example, it may be less important to submit numerous sections for a high-grade sarcoma than for a low-grade lesion in which the sampling is driven by the need to rule out the presence of high-grade areas. We generally obtain one section for each centimeter of tumor diameter, with no more than 10 sections if the lesion appears more or less uniform. Representative sections of the margins or sections designed to show the impingement of vital structures are also obtained. We select blocks for margins judiciously, depending on the gross appearance of the lesion. Lesions several centimeters away from a margin seldom have positive margins microscopically, so extensive margin sampling in these situations is less critical than excisions containing grossly close margins. Close margins should be sampled with radial sections from tumor to inked margins to be able to measure accurately the distance to the margin. One notable exception are tumors such as epithelioid sarcoma and myxofibrosarcoma; both tumors may be grossly deceptive in their clinical extent. Digital images can be useful for providing visual data as to the orientation of the specimen and sampling sites.

Most specimens are handled adequately, as described previously. In diagnostically challenging cases, it is useful to have frozen tissue in reserve if ancillary studies are required. Even though the ability to perform molecular tests on formalin-fixed material has significantly diminished the need to have fresh tissue on every case, freezing tissue is an excellent practice, particularly because frozen tissue is often a requirement for patient entry into national protocols (e.g., childhood rhabdomyosarcoma). Approximately 1 cm ³ is sufficient, although less is acceptable from small biopsy specimens. The tissue should be cut into 0.2-cm ³ fragments, stored at −70°C, and shipped on dry ice, if necessary.

The first and most important step in reaching a correct diagnosis is careful scrutiny of conventionally stained sections at low-power magnification. Useful microscopic features that can be identified at this point include the size and depth of the lesion, its relation to the overlying skin and underlying fascia, and the nature of the borders (e.g., pushing, infiltrative).

The most important decision to be made initially is whether the lesion is a benign pseudosarcomatous lesion or a sarcoma. Pseudosarcomatous lesions occur in either superficial or deep soft tissue but tend to occur more frequently superficially ( Box 5.2 ). Several histologic features suggest a pseudosarcomatous process. First, many of them display a zonation. For example, in the case of fascial forms of nodular fasciitis and ischemic fasciitis, there is a cuff of proliferating fibroblasts surrounding a central hypocellular zone of fibrinoid change. Myositis ossificans also displays zonation, manifested by centrifugal maturation of fibroblastic to osteoblastic mesenchyme. The cells of these pseudosarcomatous lesions often have the appearance of tissue culture fibroblasts, with large vesicular nuclei, prominent nucleoli, and striking cytoplasmic basophilia, reflecting the presence of abundant, rough endoplasmic reticulum. Although mitotic figures may be numerous, important negative observations include the absence of atypical mitotic figures or nuclear pleomorphism and hyperchromasia, as one would expect in a sarcoma.

When evaluating a soft tissue tumor, the architectural pattern, the appearance of the cells, and the characteristics of the stroma should be noted. These features lend themselves to the development of a number of differential diagnostic categories, as follows:

• Fasciculated spindle cell tumors. These lesions comprise a large group of tumors (e.g., adult-type fibrosarcoma, malignant peripheral nerve sheath tumor, synovial sarcoma) characterized by spindled cells arranged in long fascicles ( Box 5.3 ). Cellular schwannoma and fibromatosis must be distinguished from the others because they are nonmetastasizing tumors. Unlike the others, fibromatosis is typically a lesion of low cellularity and nuclear grade. Cellular schwannoma, unlike the others, is characterized by diffuse, intense S-100 protein, and Sox10 immunoreactivity.

  Box 5.3

  Fasciculated Spindle Cell Tumors

  • Fibromatosis (desmoid tumor)

  • Cellular schwannoma

  • Cellular perineurioma

  • Fibrosarcomatous dermatofibrosarcoma protuberans

  • Adult-type fibrosarcoma

  • Leiomyosarcoma

  • Spindle cell rhabdomyosarcoma

  • Synovial sarcoma (monophasic fibrous type)

  • Malignant peripheral nerve sheath tumor

  • Low-grade fibromyxoid sarcoma

• Myxoid tumors ( Box 5.4 ). Although almost any soft tissue tumor may appear myxoid from time to time, a number of lesions display myxoid features consistently. In adults, the differential diagnosis of myxoid tumors includes tumors such as myxoma, myxofibrosarcoma, myxoid liposarcoma, and extraskeletal myxoid chondrosarcoma. Analysis of the vascular pattern, degree of nuclear atypia, and organization of the cells aid in this distinction. For example, an intricate vasculature is a feature of both myxoid liposarcoma and myxofibrosarcoma, but it is not a feature of extraskeletal myxoid chondrosarcoma or myxoma.

  Box 5.4

  Myxoid Soft Tissue Lesions

  • Myxoma, cutaneous, intramuscular

  • Aggressive angiomyxoma

  • Superficial angiomyxoma

  • Digital fibromyxoma

  • Myxoinflammatory fibroblastic sarcoma

  • Perineurioma, myxoid

  • Neurofibroma

  • Nerve sheath myxoma

  • Chondroma

  • Spindle cell lipoma

  • Lipoblastoma

  • Lipoblastoma-like tumor

  • Low-grade fibromyxoid sarcoma

  • Ossifying fibromyxoid tumor

  • Myxoid liposarcoma

  • Extraskeletal myxoid chondrosarcoma

  • Dermatofibrosarcoma protuberans, myxoid

  • Myxofibrosarcoma

  • Botryoid embryonal rhabdomyosarcoma

  • Myxoid leiomyosarcoma (rare)

  Only gold members can continue reading. Log In or Register to continue

  Share this:

  • X
  • Facebook

  Like this:

  Like Loading…

  Related

  Related posts:

  1. General Considerations
  2. Clinical Evaluation and Treatment of Soft Tissue Tumors
  3. Fibrohistiocytic Tumors of Intermediate Malignancy
  4. Benign Vascular Tumors and Malformations

  

  Stay updated, free articles. Join our Telegram channel

  Join