Case Presentation - Spring, 2015
Written by: Written by: Emily McMeekin, student, Cleveland Clinic School of Cytotechnology, Cleveland, Ohio
Patient Age: Female, age 47
Patient History: History of Leiomyosarcoma of the thigh. Scalp cyst showed metastatic Leiomyosarcoma.
Specimen type: FNA of the Right Breast, ThinPrep® Non-Gyn cytology
Cytologic Diagnosis: Positive for malignant cells, consistent with Leiomyosarcoma
Case provided by: The lab providing this case would like to remain anonymous.
Leiomyosarcoma is a type of soft tissue sarcoma that derives from mesenchymal cell lines. Mesenchymal cells arise from undifferentiated, non epithelial mesodermal tissue, mesenchyme, and are spindle-to stellate-shaped with cellular processes that intertwine to create a network. Therefore, leiomyosarcoma is composed of distinct smooth muscle differentiation and is a relatively common sarcoma that comprises roughly 5%-15% of smooth muscle sarcomas.1,2 Three geographic groups divide leiomyosarcomas of soft tissue with location taking priority of histologic features: 1. Retroperitoneal and intra-abdominal, 2. cutaneous and subcutaneous tissue, and 3. vascular origin.1 This case reflects the second category of cutaneous and subcutaneous tissue and favors a good prognosis due to its superficial location.
Leiomyosarcomas of soft tissue do not have specific clinical diagnostic features that differentiate them from other soft tissue tumors. Persons with leiomyosarcoma are typically female and of an older age, usually 50-60 years old-probably reflecting the tumors response to estrogen.3 The most common locations are the retroperitoneum and pelvis, where patients can present with abdominal mass, pain, swelling, weight loss, nausea or vomiting. They typically occur on the extremities and have a partiality for the hair-bearing extensor surfaces.1 Leiomyosarcoma often presents as an enlarging, painless mass when it arises from somatic soft tissue. It is the most common sarcoma to form in large blood vessels and can also occur in the parenchymal organs.
Leiomyosarcomas commonly appear as gray-white and whorled with a varying degree of circumscription. If found in the dermis they look poorly defined since it can blend the tumor fascicles with neighboring collagen and pilar arrestor muscle. However, if found in subcutis the tumor will likely be circumscribed because of their ability to compress the surrounding tissue, forming a pseudocapsule.1
Treatment and Prognosis:
Treatment for localized primary extremity soft tissue sarcomas includes surgery, radiation, and chemotherapy. Surgery and radiation combined help decrease the likelihood of local recurrence.
Prognosis is reflected on a tumor’s grade, of which leiomyosarcomas can have low and high grades. Also, tumors that are less than 2.5 cm in diameter have a better prognosis than those larger. Leiomyosarcomas are graded on cellularity, degree of cytologic differentiation, mitotic count, and extent of necrosis.2 Therefore, low-grade tumors are typically more modest in cellularity, level of atypia, mitotic rates, with little to no necrosis. Fine needle aspiration (FNA) biopsy can aid in tumor grade by providing an adequate sample for the above grade qualifications. It is of note that mitotic counts are lower in FNAs than tissue sections.
Soft tissue sarcomas typically metastasize hematogenously, with the lung being the most common location of metastasis. It is also common for the tumor to metastasize to the liver, skin, soft tissue, and bone. Intradermal metastasis of leiomyosarcoma is curable if a wide excision is achieved.3
Cytologically low-grade leiomyosarcomas present with plump spindle cells that possess cigar-shaped nuclei to blunt-ended nuclei, perinuclear vacuoles, abundant cytoplasm, and myofibrils.2 Nuclear palisades are common and can suggest a neural tumor. Nuclear chromatin is variably granular and displays a characteristic striated or fishbone appearance4 with inconspicuous nucleoli. Metachromatic myxoid material or stromal fragments can be present in both benign and malignant smooth muscle tumors.5
High grade leiomyosarcomas cytologically illustrate pleomorphic changes, mitosis, and necrosis. There may be epithelioid cells, palisades, and myxoid stroma. Cells are found singly or in loose groups and vary from spindle-shaped to noticeably pleomorphic.2 Nuclei can be elongated or irregular in appearance and be single or multiple in number. Coarse irregular chromatin and prominent nucleoli are characteristic of leiomyosarcoma nuclei. The cells can also possess intranuclear cytoplasmic invaginations and variable amounts of cytoplasm.1,2,6 The tumor stains positive via immunohistochemistry for muscle markers and negative for S100 protein.2
Immunohistochemical stains are imperative in differentiating leiomyosarcoma from various other neoplasms. Epithelial markers cytokeratin and EMA are focally expressed in Leiomyosarcomas. Negative stains include CD117, S100 protein, and EMA.2
Leiomyoma is a benign smooth muscle tumor that lacks nuclear pleomorphism, mitotic activity, and necrosis. It is common to see myxoid change and focal calcification. Cytologically it is composed of spindle-shaped cells with abundant wiry, fibrillar, cytoplasm.1 They stain strongly for desmin and negative for c-kit and S100 protein.2
Nodular fasciitis is a benign smooth muscle tumor that presents with pleomorphic cells which can be round, oval, or spindle-like in shape. Bi-nuclear cells and plasmacytoid cells can be found in the background of chondromyxoid stromal fragments. The cells are arranged resembling a sheet-like pattern and fascicles with possible hyalinization and some mitosis. This tumor stains positive for vimentin and smooth muscle actin, while it stains negative for myogenin/ALK-1.7
Desmoid tumors are unique in that they do not metastasize so technically they are considered benign, but resemble malignancies in their clinical behavior, cellular biology, and molecular etiology. Cytologically they contain elongated spindle cells surrounded by collagen fibers. They stain positive for vimentin and negative for E-cadherin.8
Fibrosarcoma accounts for roughly 3% of soft tissue sarcomas and commonly arises in the extremities. Cytologically the tumor cells present in a scattered population of loose cell groups. Cells resemble spindle-shapes with hyperchromatic fusiform, ill-defined, and elongated cytoplasm. Overall the cells are roughly monomorphic with low cellularity. Fragments of dense collagenous stroma and multinucleate degenerated muscle cells are present in the background. Cells have oval to elongated nuclei with frequent crush artifact. Mitotic activity is rare. Immunohistochemically the tumor stains positive for Beta-catenin and FIM and negative for S-100, CD117, CD34, and SMA.2
Schwannomas occur in people before middle age and are typically located in the extremities and head and neck. These tumors are well differentiated and encapsulated. It is common to see nuclear palisading surrounding an eosinophilic basement membrane material and myxoid foci with dispersed spindle cells. Lymphoid aggregates with intratumoral foamy macrophages can be found in the background. They are S100 protein positive, actin and desmin-negative. Immunostains for neurofilaments can exhibit axons, thus differentiating schwannomas from leiomyosarcomas.9
Synovial sarcomas typically occur in young adults and makes up roughly 10% of all sarcomas. The most common location where it arises is in is the lower limbs, specifically the thigh. Histologically synovial sarcomas can be biphasic, composed of both spindle cell and epithelial components, or monophasic, purely spindle cell. Cytologically they display a high cellularity of two primary types of clusters: clusters alternating with dispersed cells and clusters with shaggy edges and thin, branching capillaries. Synovial sarcomas present with extreme uniformity of cells, bland oval nuclei with scant, delicate, tapering cytoplasm. Occasionally epithelial elements can be seen. Roughly one third of these tumors stain positive for S100. Almost all cases exhibit Bcl-2 positivity.10
Leiomyosarcomas can also have differential diagnosis of: inflammatory myofibroblastic tumors, solitary fibrous tumors (SFT)1, gastrointestinal stromal tumors (GIST)1, and malignant peripheral nerve sheath tumors (MPNSTs)9.
- Goldblum J. R., Folpe A. L., Weiss S. W. Enzinger and Weiss's Soft Tissue Tumors, Sixth Edition. 2014. Elsevier Inc. 402-419.
- DeMay R. The Art and Science of Cytopathology, Second Edition. 2012. American Society for Clinical Pathology. 2:636-672.
- Weaver M. J., Abraham J. A. Leiomyosarcoma of the Bone and Soft Tissue: A Review. 2007. ESUN. Sarcomahelp.org/leiomyosarcoma.html.
- Dahl I., Akerman M. Nodular fasciitis: a correlative cytologic and histologic study of 13 cases. 1981. Acta Cytol 25: 215-223.
- Hajdu S. I. Diagnosis of soft tissue sarcomas on aspiration smears (editorial). 1996. Acta Cytol 40::607-608.
- Cibas E. S., and Ducatman B. S. Cytology: Diagnostic Principles and Clinical Correlates: Fourth Edition. 2014. Elsevier Inc. 471-513. ISBN-13: 978-1455744626.
- Singh S, Paul S, Dhall K, Khichy S. Nodular fasciitis: A diagnostic challenge. Indian J Pathol Microbiol. 2013;56:288-90.
- Alman B. Desmoid Tumors: Are They Benign or Malignant? 2012. Springer Science and Buisness. 10.1007/978-94-007-1685-8_13.
- Hayat M. A. Tumors of the Central Nervous System. 2013. Springer Science and Buisness.10.1007/978-94-007-5681-6_13.
- Blackmon S., Cagle P. T., Allen T. C., Mody D. R., and Fraire A. E. Atlas of Neoplastic Pulmonary Disease: Pathology, Cytology, Endoscopy, and Radiology. 2010. Springer Science and Buisness. 81-84.
- Brennan M. F., Antonescu C. R., and Maki, R. G. Management of Soft Tissue Sarcoma. 2013. 10.1007/978-1-4614-5004-7_9.