Soft tissue tumour diagnosis: the Sarawak experience and challenges

Mohammad Zulkarnaen bin Ahmad Narihan MB BCh BAO (Ireland), MPath (UKM)

Department of Pathology Universiti Malaysia Sarawak

Soft tissue tumour

• Soft tissue refers to non-epithelial tissue excluding skeleton, joints, CNS, hematopoietic and lymphoid tissue – fat tissue, – muscles, – blood vessels – fibrous tissue

• benign soft tissue tumour outnumber malignant counterparts by 100 fold, with an exception of skeletal muscle neoplasm

• Malignant soft tissue tumour / sarcoma accounts for less than 1 % of all cancers per year

Soft tissue tumour

Benign

• Closely resemble normal tissue

• Have limited capacity for autonomous growth

• Little tendency to invade locally

• Low rate of local recurrences after conservative therapy

• Management: Most of the time Surgery is curative

Malignant • Locally aggressive • Capable of invasive or

destructive growth, recurrence and distant metastasis

• Management: – Depends on the size of the

tumour, location (deep vs superficial) and grade of the tumour

– Low grade tumours, superficial location and small sized tumour: surgery

– High grade tumours, deep seated, large size: Surgery, radiation +/- chemotherapy

• Most of the soft tissue tumour cases that are seen in the Sarawak General Hospital are benign in nature, with lipoma being the commonest diagnosis.

• The malignant tumours that are encountered in our practice range from – Leiomyosarcoma, – liposarcoma, – malignant peripheral nerve sheath tumour – Undifferentiated pleomorphic sarcoma

Soft tissue sarcoma in Sarawak musculoskeletal tumour team in 2012-13

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High Grade Sarcoma Leiomyosarcoma liposarcoma MPNST UPS

Chart Title

2012 2013

• Main pathological diagnostic methods employed in Sarawak:

– Histopathology (paraffin embedded tissues)

– Immunohistochemistry

– Frozen section

– Fine needle aspiration cytology

Histopathology

• Main diagnostic tool

• Advantage:

– Retains the architecture (vs FNAC)

– Optimal for ancillary studies (vs FNAC)

• Specimens range

– Needle core biopsies

– Incision biopsy

– Resection specimen

Challenges in Histopathology

• Needle core biopsy

1. Tissue biopsies are very small

– Negative / non- diagnotic – frequent initially

– Recommendation that at least 3 cores are sampled

2. Deep seated tumours

– Representative tissue may be difficult to reach

– Small percentage of the core biopsies may harbour tumour tissue

– Proceed to open biopsy

Challenges in Histopathology

• Excision / Resection specimen 1. Very large tumours

• Some of the tumours that we encounter are large • Optimal fixations require serial slicing of the tumours before

immersing in 10% formalin • Longer turnaround time

2. Overlapping histological features • We depend on the tissue pattern for diagnosis

– Pleomorphic cell tumours – Small round cell tunours – Spindle cell tumours – Myxoid tumours – Epitheloid tumours

• Many soft tissue tumours share tissue patterns. Only few are unique. This is where immunohistochemistry panel are important

Immunohistochemistry

• Many of the soft tissue tumour can be subtyped histologically using both H&E morphological analysis and immunohistochemical studies.

• These panel are used as first line immunohistochemical study. – Vimentin – S100 – Cytokeratin – Smooth muscle actin – Desmin

• We also employ other second line immunohistochemistry which are for more subtype specific studies such as bcl2, ck7, myogenin.

Case study

H&E Vimentin

Smooth muscle actin, CD34, S100 CD99

Challenges in Immunohistochemistry

• Even though there are a variety of immunohistochemical study that may be used, due to overlapping features, some of the soft tissue sarcoma falls under high grade sarcoma not otherwise specified.

• Discussion with the surgeons / oncologists for clinical and radiological correlation is important

Frozen section

• Main uses in soft tissue tumour – Determination of surgical margin during surgery – Confirmation of residual tumour intraoperatively – Determine enough viable tissue / representative tissue

present

• In our setting, it is not used for primary diagnosis • Frozen sections are almost always inferior in quality

than paraffin embedded sections, - misinterpretation may occur. After performing frozen section, the diagnosis is confirmed with paraffin sections

• Immunohistochemistry may be suboptimal if used on previously frozen tissue

Frozen section cases

Fine Needle Aspirate Cytology

• Advantages

– Outpatient procedure

– Low risk of complications

– Low cost

• Disadvantages

– Architecture of the tissue is lost

– FNAC samples are suboptimal for ancillary studies

Fine needle aspirate cytology

• Very difficult to categorize soft tissue tumour exactly by FNA due to – heterogenous nature of soft

tissue tumours – Absence of tissue

architecture

• Differentiation between low grade malignancy and benign lesions is also difficult – Absence of representative

cells, mitosis and arrangements (capsular invasion etc) to indicate malignancy

Molecular diagnostics

• WHO soft tissue tumours classifications has evolved from classifying the tumours using patterns to classification using molecular genetics and cytogenetics characterization

• Molecular testing has grew in importance especially with the advancement of targeted therapy

• Fortunately, immunohistochemistry has also evolved to

detect protein product of chimeric gene fusion or mutated genes

• Eg: – FLI-1 for Ewing / PNET – ALK for Inflammatory myofibroblastic tumour

• Soft tissue malignancies are rare, There are more benign tumours

• Diagnostic challenges include sampling of representative tissue, overlapping features in HPE and IHC

• Discussion with the surgeons / oncologists for clinical and radiological correlation is important

Acknowledgement

Reference

• Ashford, R.U., Scolyer, R.A., McCarthy, S.W., Bonar, S.F., Karim, R.Z. and Stalley, P.D., 2009. The role of intra-operative pathological evaluation in the management of musculoskeletal tumours. Treatment of Bone and Soft Tissue Sarcomas, pp.11-24.

• Suvarna, K.S., Layton, C. and Bancroft, J.D., 2012. Bancroft's Theory and Practice of Histological Techniques E-Book. Elsevier Health Sciences.

• Singh, Harsharan K., Scott E. Kilpatrick, and Jan F. Silverman. "Fine needle aspiration biopsy of soft tissue sarcomas: utility and diagnostic challenges." Advances in anatomic pathology 11.1 (2004): 24-37.

• Parham, D. M. (2015). Immunohistochemical Markers of Soft Tissue Tumors: Pathologic Diagnosis, Genetic Contributions, and Therapeutic Options. Analytical chemistry insights, 10(Suppl 1), 1.

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