SECTION 2 Diagnostic Approach to Soft Tissue Tumors Overview Biopsy and Resection of Soft Tissue Tumors 20 Clinical Approach Age- and Location-Based Approach to Diagnosis 24 Histologic Approach Pattern-Based Approach to Diagnosis 26 Feature-Based Approach to Diagnosis 34 Biopsy and Resection of Soft Tissue Tumors OVERVIEW ○ Aspiration allows for immediate evaluation of sampling adequacy (success or failure of attaining diagnostic General Points tissue) with added benefit of cell block for histologic and • A variety of diagnostic procedures are currently available to immunohistochemical evaluation surgeons and clinicians to evaluate soft tissue tumors ○ Popular due to minimal risk of morbidity to patient ○ Initial tumor tissue sampling may or may not be sought, • Open surgical biopsy depending on overall impression of tumor biologic ○ Small sample of tumor/lesion, but generally contains potential derived from synthesis of clinical features and more intact tissue than core needle biopsy or FNA imaging characteristics ○ Tissue may be sent for intraoperative frozen section – Tumors that appear likely benign are often surgically consultation or just permanent sectioning excised without sampling, or followed clinically ○ Smaller risk of underdiagnosis or misdiagnosis compared – Tumors that appear likely malignant or potentially to needle biopsy and FNA malignant are usually sampled preoperatively • Local excision □ With increasing frequency, soft tissue tumors are ○ Entire tumor available for histologic evaluation sampled initially by core needle biopsy, fine-needle ○ Surgical focus is on removal of tumor and not achieving aspiration (FNA), or limited biopsy due to minimal rim of uninvolved soft tissue Diagnostic Approach to Soft Tissue Tumors morbidity to the patient ○ Standard approach for benign, superficial tumors that □ Nondiagnostic results may reflex into larger open are not believed to be locally aggressive surgical biopsy with intraoperative frozen section • Resection with margins evaluation or even outright resection, depending ○ Includes wide resection and radical resection on clinical impression of tumor biology – Radical resection often contains extensive normal □ Successful diagnosis usually leads to local excision, tissue or, in cases of intraabdominal, intrathoracic, or wide resection with margins, or preoperative retroperitoneal tumors, may contain organs involved adjuvant chemotherapy &/or radiation by tumor • Smaller specimens are generally more challenging to ○ Entire tumor available for histologic evaluation evaluate due to sampling problems and issues related to ○ Standard approach for locally aggressive benign tumors immunohistochemistry (e.g., fibromatosis), deep (subfascial) tumors, and ○ Underdiagnosis often poses greater risk than sarcomas overdiagnosis ○ May be performed following chemotherapy &/or ○ Misclassification is possible if several different tumors radiation to improve resectability and decrease potential share morphologic overlap morbidity Types of Specimens BIOPSY SPECIMENS • Core needle biopsy ○ Very small sample of a tumor/lesion General Histologic Approach ○ Popular due to minimal risk of morbidity to patient • Ensure that lesional tissue is present ○ May be done in outpatient setting for superficial lesions • Evaluate histologic growth pattern and architecture in or under CT guidance for deep or visceral lesions conjunction with cytologic features of tumor cells • FNA ○ Looks for histologic clues that suggest specific ○ Very small sample of a tumor/lesion differentiation (e.g., lipoblasts) • Assess mitotic activity and presence or absence of necrosis Core Needle Biopsy Fine-Needle Aspiration (Left) Collecting tissue by core needle biopsy has become popular due to both the ease of performance and minimal morbidity to the patient as compared with open surgical biopsy. Despite the limited tissue sample, a diagnosis is often possible with careful histologic evaluation and judicious use of ancillary techniques. (Right) Cell block collected from a fine-needle aspiration (FNA) can also be used for diagnosis. However, tissue is often heavily fragmented and scant, as depicted. 20 Biopsy and Resection of Soft Tissue Tumors Diagnostic Approach to Soft Tissue Tumors • Utilize ancillary studies (e.g., immunohistochemistry, ○ e.g., "Although these findings are suggestive of a low- molecular analysis) as needed grade neoplasm such as an intramuscular myxoma, a • If constellation of features is classic for particular tumor, low-grade sarcoma such as low-grade fibromyxoid diagnosis can be made sarcoma or low-grade myxofibrosarcoma cannot be • If clear diagnosis cannot be made, determine whether excluded in this limited sample." tumor appears benign, low-grade malignant, or high-grade ○ e.g., "Although the histologic features are consistent malignant with a neurofibroma, given the large size of the lesion ○ Even in absence of clear diagnosis, this information is clinically, the possibility of an unsampled malignant helpful to guide surgical/clinical planning component cannot be excluded in this limited sample." Caveats RESECTION SPECIMENS • Always exclude carcinoma, melanoma, lymphoma, and General Histologic Approach mesothelioma before committing to a mesenchymal diagnosis • Surgical removal without neoadjuvant therapy • At times, actual tumor does not get sampled ○ If tumor has been sampled previously, review original ○ Some tumors may incite prominent peripheral host biopsy (if available) and confirm diagnosis and adequacy fibroblastic or inflammatory reaction that is of sampling inadvertently sampled – If diagnosis is established or confirmed, assure ○ Normal subcutaneous fat adjacent to tumor may be accuracy of histologic grade (if applicable) sampled and mistaken for lipomatous tumor □ Tumors diagnosed as "low grade" on biopsy may • Be wary of sampling issues related to biopsy evaluation contain higher grade areas in resection specimen ○ Tumors that appear low grade on biopsy may contain – Ancillary techniques (e.g., immunohistochemistry, higher grade areas upon resection molecular analysis) may be utilized as needed – Particularly important in tumors of adipocytic and ○ If tumor has not been sampled previously, evaluate all neural origin histologic sections of tumor to establish diagnosis ○ Tumors that appear as nonspecific high-grade – Ancillary techniques may be utilized as needed pleomorphic sarcomas on biopsy often can be more ○ Evaluate margin status (mainly sarcomas and locally specifically classified on resection aggressive benign tumors) – e.g., dedifferentiated liposarcoma, pleomorphic • Surgical removal following neoadjuvant therapy liposarcoma, extraskeletal osteosarcoma ○ If tumor has been sampled previously, review original – Diagnosis "undifferentiated pleomorphic sarcoma" biopsy (if available) and confirm diagnosis should not be made on biopsy, as it is a diagnosis of ○ Determine whether diagnosis can be established or exclusion confirmed on resection (may not be possible due to • Awareness of particular idiosyncrasies of soft tissue treatment effect) pathology is very important – Overall histologic picture depends heavily upon ○ Sarcomas may appear paradoxically bland and therefore biologic response of tumor to therapy benign □ Tumors may be extensively necrotic, inflamed, &/or – e.g., low-grade fibromyxoid sarcoma, myxoid fibrotic/hyalinized liposarcoma, myxoid synovial sarcoma □ Tumor cells may become markedly pleomorphic ○ Benign tumors may show histologic features that and atypical, including bizarre cytomorphologies suggest malignancy ○ Document approximate percentage of residual tumor – e.g., nodular fasciitis, proliferative fasciitis/myositis, viability cellular schwannoma ○ Evaluate margin status • Only commit to clear diagnosis on biopsy if it is well Caveats supported • Despite all efforts, a small percentage of soft tissue tumors ○ In general, a conservative diagnosis on biopsy better defy classification after resection serves the patient ○ Distinction between benign, low-grade malignant, and Reporting high-grade malignant should be the goal in these cases • Every effort should be taken to establish a clear diagnosis ○ Always ensure carcinoma, melanoma, lymphoma, and (and histologic grade, if applicable) on biopsy mesothelioma have been excluded before committing ○ Modern ancillary techniques are making this much easier to a soft tissue diagnosis for pathologists • Care is warranted when attempting to classify a soft tissue ○ Margin status cannot be evaluated tumor treated preoperatively with chemotherapy/radiation • If clear diagnosis cannot be established, descriptive ○ Tumors that are usually cytologically monomorphic may diagnosis can help guide surgical/clinical planning appear pleomorphic following therapy ○ e.g., benign fibroblastic lesion ○ Cytoplasmic vacuolizations may be prominent, mimicking ○ e.g., low-grade myxoid neoplasm, favor benign lipoblastic differentiation ○ e.g., high-grade pleomorphic sarcoma, not further ○ Ancillary techniques are unreliable following classified chemotherapy/radiation and should not be utilized • A descriptive comment is highly recommended in many cases to discuss differential diagnosis options 21 Biopsy and Resection of Soft Tissue Tumors Reporting Evaluation by Ancillary Testing • Surgical pathology reports for soft tissue resections should • Immunohistochemistry (IHC) contain tumor diagnosis, histologic grade (if applicable), ○ Wide array of antibodies available today has made it and margin status (if appropriate) easier