MRI is the modality of choice for detecting, characterizing, and staging STTs due to its ability to distinguish tumor tissue from adjacent muscle and fat, as well as to define relationships to key neurovascular bundles. It provides better tissue discrimination between normal and abnormal tissues than any other imaging modality. In addition, it aids in guiding biopsy, planning surgery, evaluating response to chemotherapy, restaging, and in the long-term follow-up for local recurrence. MRI accurately defines tumor size and provides information on hemorrhage, necrosis, edema, cystic and myxoid degeneration, and fibrosis. Soft tissue masses that do not demonstrate tumor-specific features on MRI should be considered indeterminate, and biopsy should always be obtained to exclude malignancy.

In MRI-guided biopsy , caution has to be excised in three respects for indeterminate STTs: selection of an appropriate pathway, coordination with the treating surgeon, and participation of a pathologist comfortable with interpreting percutaneous biopsies. The radiologist should undertake the biopsies only at the request of the treating surgeon and not necessarily at the request of the patient’s initial physician. In collaboration with the treating surgeon, the needle tract (which needs to be excised with the tumor) can be established and the patient well served .

Spiral CT is preferable for examining sarcomas of the chest and abdomen, since air/tissue interface and motion artifacts often degrade MRI quality. A baseline chest CT scan at the time of the diagnosis for evidence of lung metastasis is important, particularly for sarcomas >5 cm, for accurate staging of patients.

Early studies suggest that positron emission tomography (PET) has clinical potential by determining biological activity of soft tissue masses. It can be used to distinguish benign tumors from high-grade sarcomas, pretreatment grading of sarcomas, and evaluation of local recurrence.

A biopsy is necessary and appropriate to establish malignancy, to assess histologic grade, and to determine the specific histological type of sarcoma given the prognostic and therapeutic importance of accurate diagnosis. A treatment plan, if it is possible, can be designed that is tailored to a lesion’s predicted pattern of local growth, risk of metastasis, and likely sites of distant spread. A large enough sample from a viable area of sarcoma is usually required for definitive diagnosis and accurate grading. Most limb masses are generally best sampled through a longitudinally oriented incision, so that the entire biopsy tract can be completely excised at the time of definitive resection. An incisional biopsy with minimal extension into adjacent tissue planes is the ideal approach for most extremity masses. Excisional biopsy should be avoided, particularly for lesions greater than 2 cm in size, since such an approach will make definitive reexcision more extensive due to the contamination of surrounding tissue planes. For deep-seated lesions, a core biopsy approach may be used to establish a diagnosis; however, the limited tissue obtained with this technique may make definitive grading and prognostication difficult. FNA cytology of STTs might be desirable to large specialty centers with a well-integrated multidisciplinary team, since careful clinicoradiologic correlation and considerable experience are required in order to make accurate diagnoses, but most patients are first seen in smaller community practices. A systematic approach to differential diagnosis, specimen triage, recommendations, and referrals can enhance the efforts of the cytopathologist, regardless of level of experience.

Sampling error is a problem which FNA shares with core and even incisional biopsies. Rapid evaluation and triage for ancillary studies such as immunohistochemistry (IHC), flow cytometry, cytogenetics, and electron microscopy (EM) are often indispensable for definitive classification and can decrease the inadequate rate. Criteria for specimen adequacy can reduce the rate of false-negative cases, but any clinically suspicious lesion should be further evaluated by biopsy. The three main reasons for a false diagnosis are sampling error, technically inferior material, and misinterpretation. Concern over needle tract seeding, stemming from the era of larger needles, however, is unfounded . See Table 10.1.

FNA of STTs is cost-effective and the least invasive method of sampling a heterogeneous lesion and does not compromise tissue planes for a subsequent excision. The indications of FNA include (1) screening, (2) primary diagnosis (although not widely accepted by most soft tissue pathologists for primary classification of sarcomas), and (3) detection of recurrence.

Ideally, one makes a separate pass for each desired ancillary study. Papanicolaou-stained slides highlight nuclear details, while Romanowsky-type stains highlight cytoplasmic details and matrix material. Thin-layer preparations offer good nuclear detail, optimize results from aspirates carried out without the benefit of rapid evaluation, and can be used for adjunct studies. However, cells appear smaller, rounder, and falsely epithelioid, and useful background information (e.g., vascular patterns) is sometimes lost .

As with other cytologic specimens, there should be a general category: malignant, suspicious, atypical, benign, and nondiagnostic. Because most STTs are treated by wide surgical excision, lack of a specific histologic subtype may not affect management. When a histologic subtype is not possible, a descriptive diagnosis should be used.

The most important prognostic consideration is the histologic grade, and most neoplasms are amenable to grading. A two-tiered grading system of low versus high is probably sufficient in the majority of cases.

Low-grade lesions have mild nuclear atypia, minimal or absent necrosis, low cellularity with minimal nuclear overlap, and rare or absent mitoses (<3/10HPF). High- grade lesions have moderate to severe nuclear atypia, intermediate to high cellularity with conspicuous to prominent nuclear overlap, definite necrosis, and frequent mitoses.

The presence or absence of mitoses and necrosis is an objective finding worthy of separate mention in the report. When only smears are available, a statement such as “mitoses are absent” or “mitoses are numerous” suffices to avoid falsely high or low counts.

Finally, most cytology reports should include a comment to address the differential diagnosis , suggest ancillary studies in equivocal cases, or advise on appropriate subsequent management.

Ancillary studies include electron microscopy (EM) , immunohistochemistry (IHC) (Table 10.2), flow cytometry, and cytogenetics.

EM is especially helpful in classifying poorly differentiated high-grade lesions and small round blue cell tumors. Cell block sections are preferred for IHC stains, but air-dried or thin-layer preparations may also be used. Flow cytometry is useful when lymphoma is suspected on rapid on-site evaluation.

An increasing number of reproducible, relatively specific cytogenetic abnormalities are identified with routine chromosomal analysis, fluorescence in-situ hybridization (FISH), and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques.

Conventional chromosomal analysis offers the advantages of a full karyotype counterbalanced by low sensitivity and long turnaround time.

FISH accurately labels targeted chromosomal regions. Cytologic specimens provide ideal substrates with intact cells and nuclei free of sectioning artifact and truncation. A moderately cellular, evenly spread preparation, such as cytocentrifuge or thin-layer preparations, is key. As only a specified chromosomal abnormality is targeted, a negative result provides little information.

In 2013, with the new genetic data, the World Health Organization (WHO) published an updated, more reproducible classification of tumors of the soft tissue. Based on the methods that the experts use and focus on visual pattern recognition to formulate a diagnosis by using concise text and an algorithmic method to make arriving at a diagnosis efficient, we put the common STTs into the following major practical categories for cytopathology of FNA specimens Table 10.3.

The benign lesions in this group produce cytologic specimens compromised of intact tissue fragments with few or no individual cells, while the malignant lesions features more discohesiveness, hypercellularity, necrosis, and mitotic activity. In addition to the distinction between benign and malignant, a frequent problem run into within this class is determining whether a lesion is of smooth muscle or nerve sheath origin. Sarcomatoid carcinoma and melanoma are always in the differential diagnosis.