Cytopathology Case 16: FNA and Core Biopsy Diagnosis of a Retroperitoneal Mass

Final Diagnosis & Discussions:

FINAL DIAGNOSIS: Leiomyosarcoma

DISCUSSION
Leiomyosarcoma is a malignant neoplasm showing smooth muscle differentiation. The tumor usually occurs in middle-aged or elderly persons, but can occur in the young. It usually develops in the retroperitoneum or pelvis, and is the most common sarcoma arising from large blood vessels (more commonly venous). A less common site of involvement is in the limb. There is a female predominance when the location is retroperitoneal or arising from the inferior vena cava, which leads some to speculate hormonal influence.

Soft tissue leiomyosarcoma presents as a mass which may be painful. If arising from the inferior vena cava, it may cause venous obstruction resulting in Budd-Chiari syndrome, renal dysfunction or lower extremity edema, depending on exact location.

Leiomyosarcomas can be divided histologically into low-grade and high-grade. In cytology smears, low grade tumors yield cohesive fascicles of fairly monomorphous, blunt- ended spindle cells (shaped like a cigar or sausage) with indistinct cell borders. Nuclei may show indentation, and nucleoli are generally inconspicuous. Cytoplasm may show fine granularity or longitudinal cytoplasmic striations, representing myofilaments. Metachromatic myxoid material or stromal fragments can also be seen in smooth muscle tumors (as was seen in this case). Cellularity is variable, but, overall, low grade lesions are less cellular than high grade. Single cells are sparse, but naked nuclei may be numerous. Lower grade lesions are more likely to exhibit clusters of cells, whereas higher grade lesions show more discohesion. High grade leiomyosarcomas can feature more epithelioid morphology and greater pleomorphism, which can make categorizing them as being of smooth muscle origin more difficult.

Many different “spindle cell lesions” enter into the cytologic differential diagnosis in a low grade leiomyosarcoma. Nuclear palisading is common, and this feature may be mistaken for nerve sheath origin (eg: schwannoma). In general, however, neural tumors have “wavy” nuclei with pointed ends. Perinuclear cytoplasmic vacuoles may be present, and may be mistaken for lipoblasts raising the possibility of a lipomatous tumor/liposarcoma, especially given the commonly shared locations of retroperitoneum and limb. Monophasic synovial sarcoma can also present as a spindle cell proliferation; however, the history is typically a mass near a large joint of a young adult. Gastrointestinal stromal tumor (GIST) shares similar features: nuclear palisading, intersecting fascicles and perinuclear vacuoles. One helpful feature is association with the wall of the stomach or intestine; however, in a large mass compressing adjacent organs this may be difficult to discern. Solitary fibrous tumor (SFT) classically arises in the pleura but can be found in any soft tissue or visceral location, and may be associated with hypoglycemia due to insulin-like growth factor production by the tumor. SFT also contains abundant collagenous stroma, a feature not observed in the current case. Additionally, intra-abdominal fibromatoses (desmoid tumors) also have bland spindle cell cytologic features that overlap with low grade leiomyosarcoma. Subtle clues to this entity are tapering cytoplasmic processes, low cellularity, and dense collagenous stroma. Another category of lesion that may enter the differential are inflammatory myofibroblastic tumors. These are generally of high cellularity, and in addition to the spindle cell proliferation show a prominent inflammatory infiltrate. Finally, a benign leiomyoma, especially benign metastasizing leiomyoma, is also a possibility. It should be noted that benign leiomyomas of the deep soft tissue are extremely rare with respect to their malignant counterpart. Features of high cellularity, hyperchromasia, significant nuclear atypia, mitoses and necrosis all favor malignancy; however, these features may be inobvious as in the current case of low grade leiomyosarcoma. Overall, many of the distinctions between the above lesions/neoplasms are subtle and more often than not, the cytodiagnosis will remain broad (“low grade spindle cell lesion”) in the absence of histology (such as a biopsy) demonstrating architecture or ancillary testing such as immunohistochemistry.

Because of the broad differential diagnosis on aspirate smears, tissue cores were obtained. By revealing intersecting fascicles of spindle cells with eosinophilic and somewhat fibrillar cytoplasm as well as occasional vacuolaization, the histologic features were in keeping with a smooth muscle tumor. In larger tumors, hyalinization and necrosis are frequently observed. The nuclei showed hyperchromasia, enlargement, and irregular contours. In conjunction with focal mitotic activity, the findings were consistent with a low grade leiomyosarcoma.

Immunohistochemical stains can also be invoked to clarify the diagnosis. Both leiomyomas and leiomyosarcomas are positive for smooth muscle markers desmin, SMA, and MSA. The other tumors in the differential show different immunoprofiles: desmoid tumors yield positive nuclear B-catenin staining, nerve sheath tumors show positivity for S100, solitary fibrous tumors are positive for CD34 and bcl-2, GISTs are usually positive for ckit, CK34, and DOG1, and synovial sarcoma is usually positive for EMA, cytokeratin, and CD99. As always, caution must be used when immunohistochemistry is utilized; as up to a third of leiomyosarcomas will show cytokeratin or EMA expression.

Leiomyosarcomas tend to have a poor prognosis and will both locally recur and metastasize. The most important factors are tumor location and size. Retroperitoneal leiomyosarcomas are usually large (>10 cm) and difficult to excise with clear margins. Those arising from large vessels are also difficult to control. Those arising from the soft tissue of the limbs are usually diagnosed at a much smaller size and are easier to resect, resulting in lower recurrence rate and fewer metastases, and thus, better overall survival. Metastases usually occur in lung and liver, less commonly in skin and bone, and rarely in lymph nodes.

References

1. Richard M. DeMay. The Art & Science of Cytopathology. 2nd ed. ASCP Press. 2012.
   
   
2. Christopher D.M. Fletcher, K. Krishnan Unni, Fredrik Mertens, ed. WHO Classification of Tumours: Tumours of Soft Tissue and Bone. IARC Press, Lyon. 2002.
   
   
3. Edmund S. Cibas and Barbara S. Ducatman. Cytology Diagnostic Principles and Clinical Correlates. Saunders Elsevier. 2009.