mgh:cyto-1-16

1-16 Bone and Soft Tissue Cases: I Chebib MD, D Kuebler CT

Indications for cytology examination

The evaluation of a soft tissue mass by fine needle aspiration remains controversial. There are a number of reasons for this that include:

1) Soft tissue tumors are relatively rare and sarcomas are generally only treated at tertiary care centers;

2) Cytopathologists without a background in soft tissue and bone pathology may be uncomfortable with interpretation of these rare specimens;

3) There is general perception that soft tissue tumors, especially benign and low-grade lesions do not yield sufficient tissue for interpretation and ancillary testing;

4) A growing number of soft tissue tumors have very similar cytomorphologic features that cannot be adequately differentiated on cytology or even histology alone;

5) There is also a growing number of ancillary tests (immunohistochemistry, fluorescence in situ hybridization, cytogenetics, electron microscopy, polymerase chain reaction) required for the appropriate categorization of soft tissue tumors. Cytology may not yield sufficient tissue for the growing array of ancillary tests needed.

6) Not uncommonly, soft tissue tumors may require the opinion of pathologists with expertise in bone and soft tissue pathology who themselves may not be comfortable with interpretation of cytology specimens.

7) Many deep soft tissue and bone tumors are biopsied by interventional musculoskeletal radiologists who may not be trained or experienced in procuring appropriate cytology specimens;

Despite these concerns, there are many situations where fine needle aspiration (FNA) biopsy of soft tissue or bone tumors may be appropriate. The most common situations for FNA biopsy of soft tissue and bone tumors include:

1) Clinical/radiologic impression of metastatic carcinoma, melanoma or high-grade lymphoma to bone or soft tissue. Cytology for epithelial, melanocytic or high-grade lymphoproliferative malignancy has been well established and interpretation by a cytopathologist is relatively straightforward if sufficient material can be procured. Many of these situations require biopsy by interventional radiology and the use of rapid on-site evaluation (ROSE) assists in ensuring these specimens have sufficient diagnostic tissue for interpretation.

2) FNA biopsy in patients with a previously established sarcoma diagnosis. In these patients, a known diagnosis aids in the interpretation of sarcomas of bone, soft tissue, lung etc. where metastasis from a known sarcoma primary may be aspirated to confirm metastasis. Comparison to the previous surgical pathology specimen of the primary sarcoma aids in interpretation of these specimens and typically does not require the addition of a large number of ancillary tests.

3) FNA biopsy of primary soft tissue and bone tumors. This situation, as addressed above, is the most controversial. However, in some situations, this may be the most viable option. Superficial tumors may be sampled in an FNA clinic relatively quickly, not necessarily to establish a specific diagnosis but to triage the patient to a general category: infectious versus neoplastic, benign versus malignant, or even morphologic subcategorization: spindle cell versus small round blue cell versus epithelioid versus pleomorphic etc. Finally, soft tissue and bone tumors can be biopsied via FNA for primary diagnosis, if the appropriate tissue is available for ancillary testing.

References

1. Kilpatrick SE1, Cappellari JO, Bos GD, Gold SH, Ward WG. Is fine-needle aspiration biopsy a practical alternative to open biopsy for the primary diagnosis of sarcoma? Experience with 140 patients. Am J Clin Pathol. 2001 Jan;115(1):59-68.

2. Liu K1, Layfield LJ, Coogan AC, Ballo MS, Bentz JS, Dodge RK. Diagnostic accuracy in fine-needle aspiration of soft tissue and bone lesions. Influence of clinical history and experience. Am J Clin Pathol. 1999 May;111(5):632-40.

3. Khalbuss WE1, Teot LA, Monaco SE. Diagnostic accuracy and limitations of fine-needle aspiration cytology of bone and soft tissue lesions: a review of 1114 cases with cytological-histological correlation. Cancer Cytopathol. 2010 Feb 25;118(1):24-32.

4. Singh HK1, Kilpatrick SE, Silverman JF. Fine needle aspiration biopsy of soft tissue sarcomas: utility and diagnostic challenges. Adv Anat Pathol. 2004 Jan;11(1):24-37.

5. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (eds.): WHO Classification of Tumours of Soft Tissue and Bone, 4th Edition. IARC: Lyon 2013.

Procuring the specimen

Soft tissue tumors may present as superficial (skin, subcutaneous) or deep (fascial, intramuscular, visceral). Superficial tumors may be biopsied by palpation readily by cytopathologists trained in FNA technique. In fact, aspiration of superficial tumors by a cytopatholigsts trained in FNA allows for immediate assessment of cellularity and typically procurement of sufficient tissue for ancillary testing. However, deep tumors of soft tissue or bone generally require image-guided FNA by interventional radiology. Rapid on-site assessment (ROSE) is very useful in these circumstances, as these tumors are often difficult to obtain sufficient material for interpretation. Bone tumors often require violation and passage of a biopsy needle through cortical bone to achieve sufficient exposure of a medullary tumor, which often complicates the biopsy procedure.

References

1. Kilpatrick SE1, Cappellari JO, Bos GD, Gold SH, Ward WG. Is fine-needle aspiration biopsy a practical alternative to open biopsy for the primary diagnosis of sarcoma? Experience with 140 patients. Am J Clin Pathol. 2001 Jan;115(1):59-68.

2. Liu K1, Layfield LJ, Coogan AC, Ballo MS, Bentz JS, Dodge RK. Diagnostic accuracy in fine-needle aspiration of soft tissue and bone lesions. Influence of clinical history and experience. Am J Clin Pathol. 1999 May;111(5):632-40.

3. Khalbuss WE1, Teot LA, Monaco SE. Diagnostic accuracy and limitations of fine-needle aspiration cytology of bone and soft tissue lesions: a review of 1114 cases with cytological-histological correlation. Cancer Cytopathol. 2010 Feb 25;118(1):24-32.

4. Singh HK1, Kilpatrick SE, Silverman JF. Fine needle aspiration biopsy of soft tissue sarcomas: utility and diagnostic challenges. Adv Anat Pathol. 2004 Jan;11(1):24-37.

5. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (eds.): WHO Classification of Tumours of Soft Tissue and Bone, 4th Edition. IARC: Lyon 2013.

Test platforms/specimen processing and triage

FNA of primary soft tissue of bone not only require well prepared and stained alcohol-fixed or air-dried smears but also sufficient material must be procured for cell block preparation, as most primary soft tissue and bone tumors require the judicial use of immunohistochemistry and molecular studies for a definitive diagnosis, with few exceptions. However, communication with the clinician may be helpful as exact subtyping of the tumor may not be required for treatment - FNA may be used as a preliminary assessment for patient triage: ie. infectious/inflammatory versus neoplastic; carcinoma or lymphoma versus sarcoma; benign versus malignant soft tissue tumor, etc. In these situations, a cytomorphologic assessment only may be sufficient to appropriately triage, and in some cases, treat the patient. However, whenever possible, cell block material should be created for potential future requirements and analysis.

References

1. Kilpatrick SE1, Cappellari JO, Bos GD, Gold SH, Ward WG. Is fine-needle aspiration biopsy a practical alternative to open biopsy for the primary diagnosis of sarcoma? Experience with 140 patients. Am J Clin Pathol. 2001 Jan;115(1):59-68.

2. Liu K1, Layfield LJ, Coogan AC, Ballo MS, Bentz JS, Dodge RK. Diagnostic accuracy in fine-needle aspiration of soft tissue and bone lesions. Influence of clinical history and experience. Am J Clin Pathol. 1999 May;111(5):632-40.

3. Khalbuss WE1, Teot LA, Monaco SE. Diagnostic accuracy and limitations of fine-needle aspiration cytology of bone and soft tissue lesions: a review of 1114 cases with cytological-histological correlation. Cancer Cytopathol. 2010 Feb 25;118(1):24-32.

4. Singh HK1, Kilpatrick SE, Silverman JF. Fine needle aspiration biopsy of soft tissue sarcomas: utility and diagnostic challenges. Adv Anat Pathol. 2004 Jan;11(1):24-37.

5. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (eds.): WHO Classification of Tumours of Soft Tissue and Bone, 4th Edition. IARC: Lyon 2013.

Reporting and terminology

The reporting of primary soft tissue and bone FNA has not been formalized, like in some other organ systems. In general, a 5-tiered interpretation system is used: non-diagnostic, benign, atypical, suspicious and malignant. However, there are many situations where a clear interpretation may not be possible: definitive neoplastic cells but unclear whether benign or malignant; in these situations "neoplastic cells present" may be used. If the specific subtype of soft tissue tumor is or may be required, production of a cell block is a necessity. Definitive subtyping of the soft tissue or bone tumor typically follows the WHO Classification of Tumours of Soft Tissue and Bone, Fourth Edition (2013).

References

1. Kilpatrick SE1, Cappellari JO, Bos GD, Gold SH, Ward WG. Is fine-needle aspiration biopsy a practical alternative to open biopsy for the primary diagnosis of sarcoma? Experience with 140 patients. Am J Clin Pathol. 2001 Jan;115(1):59-68.

2. Liu K1, Layfield LJ, Coogan AC, Ballo MS, Bentz JS, Dodge RK. Diagnostic accuracy in fine-needle aspiration of soft tissue and bone lesions. Influence of clinical history and experience. Am J Clin Pathol. 1999 May;111(5):632-40.

3. Khalbuss WE1, Teot LA, Monaco SE. Diagnostic accuracy and limitations of fine-needle aspiration cytology of bone and soft tissue lesions: a review of 1114 cases with cytological-histological correlation. Cancer Cytopathol. 2010 Feb 25;118(1):24-32.

4. Singh HK1, Kilpatrick SE, Silverman JF. Fine needle aspiration biopsy of soft tissue sarcomas: utility and diagnostic challenges. Adv Anat Pathol. 2004 Jan;11(1):24-37.

5. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (eds.): WHO Classification of Tumours of Soft Tissue and Bone, 4th Edition. IARC: Lyon 2013.

Basic cytomorphology

Gout – MN09-F8915

• Right foot FNA
• Background of amorphous material with scattered histiocytes and multinucleated giant cells
• Polarizable needle shaped crystals seen within the amorphous material
• The findings are consistent with tophus (chronic gout) and the crystals are composed of uric acid
• Compare the appearance of the air dried smear (most cells appear larger in size) to the ethanol fixed Papanicolaou stained smear.

Chordoma – MN09-D13495

• Bone mass at C-3
• Smear is moderately cellular
• Sheets of large cells with vacuolated cytoplasm
• Round to ovoid nuclei
• Inconspicuous nucleoli
• Physaliferous cells along with the second component of neoplastic cells are smaller with an epithelioid appearance and moderate amounts of an eosinophilic and granular cytoplasm
• The nuclei found in both cell types are variable in size and shape, nucleoli can be prominent
• Mitotic figures are rare
• Marked nuclear hyperchromasia is not present
• A chordoma should always be considered in any soft tissue/ bone/ mass that one encounters

• Pelvic chordomas can present as large lytic lesions in the sacrum and others presenting in the shpeno-occipital area present at a smaller size- these are slow growing malignant tumors

• Chordomas are cytokeratin positive, are reactive with antibodies against epithelial membrane antigen and also S-100 protein

Myxoid liposarcoma – N13-1062

• Shoulder mass FNA
• Smears contain numerous elongated spindle shaped or ovoid nuclei with pale chromatin
• Pale, delicate cytoplasm, mitoses are absent
• Branching and interlacing so called chicken wire network of small vessels present
• Myxoid material staining on the Giemsa stained smear

Ewing’s Sarcoma – S90-b11855

• Leg mass, smear of tumor
• Classic features of Ewing’s include cellular features with single cells and loose clusters, two cell types, large pale cells with vacuolated cytoplasm and small dark cells with scant cytoplasm
• Numerous naked nuclei due to fragile cytoplasm, and occasional rosette-like structures
• The DDX includes other small cell neoplasms such as lymphoma, neuroblastoma, and small cell carcinoma
• Clinical presentation and patient’s gender and age can assist in making the accurate diagnosis
• This patient’s age is unusual for the typical round cell tumors

Giant cell tumor of bone – 91-12413

• Iliac crest FNA
• Groups of spindly cells with scant cytoplasm and uniform oval nuclei with smooth chromatin
• Multinucleated giant cells with uniform small nuclei (a dozen or more but are fairly uniform in size)
• Mitotic figures may be present
• The nuclei have condensed chromatin with small but distinct nucleoli

Metastatic Lobular Carcinoma of the breast – MN10-4291

• Loosely cohesive small-medium epithelial cells with abundant cytoplasm eccentrically placed oval (sometimes indented) nuclei, and finely granular chromatin
• Several signet ring cells with large cytoplasmic vacuole displacing the nucleus to the side