Journal of Cytology
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SYMPOSIUM Table of Contents   
Year : 2008  |  Volume : 25  |  Issue : 3  |  Page : 93-96
Cytology of soft tissue tumors: Pleomorphic sarcoma


Department of Pathology, Lady Hardinge Medical College, New Delhi - 110 001, India

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How to cite this article:
Jain M, Malhan P. Cytology of soft tissue tumors: Pleomorphic sarcoma. J Cytol 2008;25:93-6

How to cite this URL:
Jain M, Malhan P. Cytology of soft tissue tumors: Pleomorphic sarcoma. J Cytol [serial online] 2008 [cited 2017 Sep 23];25:93-6. Available from: http://www.jcytol.org/text.asp?2008/25/3/93/44040



   Introduction Top


Pleomorphic cell tumors constitute approximately 10-15% of all soft tissue tumors. They are characterized by variably sized and shaped cells, often including multinucleate giant cells with atypical nuclei. Although pleomorphism in a soft tissue tumors is usually suggestive of a sarcoma, it is not always so. This morphological group of tumors also includes benign pseudosarcomatous lesions and malignant nonsarcomatous tumors. A relevant clinical history, adequate tumors sampling, and immunohistochemical evaluation helps in differential diagnosis.

Until recently, a subclassification of pleomorphic sarcomas was regarded as a mere academic exercise. But now, it has been unequivocally demonstrated that accurate histological subtyping is clinically relevant as it allows for the recognition of nonsarcomatous lesions and permits the identification of subsets of pleomorphic sarcoma with especially unfavorable prognosis. [1]

Accurate subclassification is hence worthwhile for-

  • Separation of true sarcomas from carcinomas, melanomas, and lymphomas showing sarcomatoid or pleomorphic morphology; which is extremely important therapeutically and prognostically.
  • Identification of subgroups with particularly dismal prognosis, such as the ones showing myogenic differentiation. [2],[3]


The evolution of the classification of pleomorphic sarcomas represents a prototype of conceptual advances generated by immunophenotyping and conventional morphology. Historically, the term, "malignant fibrous histiocytoma (MFH)" was introduced in 1963 by Ozello, O'Brien, and Stout; and it represented the most frequently diagnosed sarcoma accounting for approximately 40% of all adult mesenchymal malignancies. [4],[5],[6]

The latest WHO classification has clearly indicated that MFH is a morphological pattern rather than a distinct clinicopathological entity. [7] It represents a synonym for undifferentiated, pleomorphic sarcomas showing no line of differentiation. [8] Even the most recent gene profiling studies have confirmed the validity of this conceptual shift. [9] Tumors exhibiting pleomorphic morphology are shown in [Table 1].


   Diagnostic Approach Top


  1. The correlation with clinical data is extremely important.

    Tumor site
    Limbs:
        Unclassified pleomorphic sarcoma ('MFH")
        High-grade myxofibrosarcoma
        Leiomyosarcoma
        Liposarcoma (pleomorphic or dedifferentiated)
        Rhabdomyosarcoma
    Extremities:
        Giant cell tumors of tendon sheath
    Retroperitoneum:
        Dedifferentiated liposarcoma
        Leiomyosarcoma
    Tumors size
        Pleomorphic sarcomas are usually larger than 5 cm at the time of diagnosis
    Age
    Young adults:
        Giant cell tumors of the tendon sheath
        Benign fibrous histiocytoma
    Elderly:
        Unclassified pleomorphic sarcoma ('MFH")
        High-grade myxofibrosarcoma
        Leiomyosarcoma


  2. Extensive sampling is mandatory for the identification of small, more differentiated areas.


  3. Immunohistochemistry aids in differential diagnosis [Table 2].



   Salient Clinicopathological Features of Various Pleomorphic Sarcomas Top


Undifferentiated pleomorphic sarcoma not otherwise specified (e.g., pleomorphic and storiform MFH)

This is defined as a group of pleomorphic, high-grade sarcomas in which any attempt to disclose their line of differentiation has failed. It constitutes ≤ 5% of all sarcomas in adults [10] and usually occurs in the extremities (lower limbs), most commonly in the sixth and seventh decades of life.

Microscopically, it exhibits cells showing marked pleomorphism admixed with bizarre giant cells, spindle cells, and variable foamy cells. Immunohistochemically, it shows 'only vimentin' phenotype along with scattered SMA (smooth muscle actin)-positive cells.

Myxofibrosarcoma (e.g., myxoid MFH)

It is one of the most common sarcomas in elderly patients with a metastatic rate of 30-35%.

It usually occurs in limb and limb girdles with the trunk/head, and neck/acral sites being much rarer.

Microscopically, it exhibits a wide spectrum of cellularity and pleomorphism. The low-grade forms show stellate cells with atypical, hyperchromatic nuclei in a myxoid stroma having thin-walled, acriform blood vessels. Pseudolipoblasts may be variably present. The high-grade forms have morphological overlap with so-called MFH showing hypercellular proliferation of spindle and pleomorphic cells (at least focally). Immunohistochemically, it shows 'only vimentin' phenotype along with few SMA (smooth muscle actin)-positive cells.

Pleomorphic sarcoma showing myogenic differentiation

Both leiomyosarcoma and rhabdomyosarcoma can display a pleomorphic phenotype.

Pleomorphic leiomyosarcoma

Pleomorphic leiomyosarcoma usually occurs in the retroperitoneum and less commonly in the limbs, in middle aged/older patients. Microscopically, the presence of better differentiated areas comprising of fascicles of spindle cells with fibrillary eosinophilic cytoplasm are a useful diagnostic clue. Immunohistochemically, it shows SMA and h-caldesmon positivity.

Pleomorphic rhabdomyosarcoma

Pleomorphic rhabdomyosarcoma commonly occurs in the deep soft tissues of the lower limbs, usually in the sixth decade of life. Microscopically, the presence of large spindled/polygonal cells with striking cytoplasmic eosinophilia clinches the diagnosis. Immunohistochemically, it is positive for desmin, myogenin, and myoglobin.

Both pleomorphic leiomyosarcoma and rhabdomyosarcoma behave as high-grade sarcomas associated with the poorest outcome among high-grade pleomorphic sarcomas. The five-year metastatic rate is 60-70% for leiomyosacomas and 90-100% for rhabdomyosarcomas. [11],[12]

Pleomorphic liposarcoma

It is the rarest variant of liposarcoma with a metastatic rate of 30-50%. [13],[14] It occurs most commonly in the sixth decade of life in the lower extremities (thigh) followed by the upper extremities and retroperitoneum.

Microscopically, it is a nondistinctive, high-grade pleomorphic/spindle cell sarcoma, the main diagnostic clue being the presence of lipoblasts. On immunohistochemistry, S-100 positivity is seen in lipoblasts.

Dedifferentiated liposarcoma

It represents a transition from a well differentiated liposarcoma to a nonlipogenic sarcoma. The dedifferentiated area may resemble an undifferentiated pleomorphic sarcoma or a myxofibrosarcoma. A few (5-10%) of these cases may show heterologous elements (myo/osteo/chondro/angiosarcomatous). It is much less aggressive with a metastatic rate of 15-20% and a long-term survival rate not significantly worse than an ordinary well differentiated liposarcoma.

Extraskeletal osteosarcoma

It may rarely exhibit a pleomorphic morphology. This variant is highly aggressive with a five-year survival rate of 25% and it occurs most commonly in the limbs of the elderly. Microscopically, it comprises of spindle/round/epithelioid/pleomorphic cell types. The presence of malignant osteoid produced by malignant cells is the main diagnostic clue.

Malignant peripheral nerve sheath tumor

It is associated with Von Recklinghausen's disease in approximately 50% of the cases. Many arise from preexisting plexiform neurofibromas. Microscopically, it is a spindle cell, fascicular neoplasm showing tapering nuclei and perivascular accentuation. A minority exhibit striking pleomorphism, this variant being aggressive with a five-year survival rate of 35% (related to histological grade).

The benign lesions that may mimic pleomorphic sarcoma are listed in [Table 3]. The relatively common ones are discussed below.

Spindle cell/Pleomorphic lipoma


It occurs in the subcutaneous tissue of the posterior neck and shoulder area in patients over 55 years of age (90% being males).

Microscopically, it is a well circumscribed tumor comprising of an admixture of mature adipocytes and bland spindle cells in short fascicles along with thick, brightly eosinophilic collagen bundles, abundant mast cells, and a variable number of bizarre, often multinucleated cells with hyperchromatic nuclei (floret cells). Myxoid change may be prominent. Immunohistochemically, it shows CD 34 positivity.

Atypical fibroxanthoma

It is a controversial tumors, variably regarded as a cutaneous variant of so-called 'MFH' or as a benign, ultraviolet-related, pseudosarcomatous lesion. It commonly occurs in the head and neck region in the elderly.

Microscopically, it is a superficial lesion with very limited involvement of subcutis. It has a smooth, deep margin which tends to push down degenerate elastic fibres and adnexa. It exhibits pleomorphic cells with abnormal mitotic figures with no perineurial/vascular invasion. Immunohistochemically, it is CD99-positive (the diagnostic value needs to be confirmed), and cytokeratin- and S-100-negative.

Proliferative fasciitis/myositis

Proliferative fasciitis occurs commonly in the lower limbs. Proliferative myositis usually involves the shoulder girdle and the upper trunk in the elderly. Microscopically, there is a spindle cell proliferation with large ganglion cells having abundant, amphophilic cytoplasm and one or more large vesicular nuclei. In proliferative myositis, the extension between skeletal muscle cells produces the characteristic checker board pattern. The lesions show focal positivity for smooth muscle actin (SMA).

Pleomorphic hyalinizing angiectatic tumors

It is seen in the subcutaneous tissue of the lower extremities in middle-aged patients. Microscopically, it shows proliferation of spindle and pleomorphic cells with bizarre, hyperchromatic nuclei having intranuclear pseudoinclusions; mitosis is rare. The background comprises of ecstatic, thin-walled vessels surrounded by prominent eosinophilic fibrin/collagen/haemosiderin deposition, organized intravascular thrombi, chronic inflammatory cells, and mast cells. The spindle/pleomorphic cells are negative for S-100 and vascular markers.


   Conclusion Top


Accurate recognition of different histological subtypes of pleomorphic sarcomas is a prerequisite which permits the identification of subsets with an especially unfavorable prognosis, thereby allowing stratification to a more aggressive and effective therapy.

 
   References Top

1.Tos AP. Classification of pleomorphic sarcomas: Where are we now? Histopathology 2006;48:51-62.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Fletcher CD, Gustafson P, Rydholm A, Willιn H, Akerman M. Clinicopathologic re-evaluation of 100 malignant fibrous histiocytomas: Prognostic relevance of subclassification. J Clin Oncol 2001;19:3045-50.  Back to cited text no. 2    
3.Deyrup AT, Haydon RC, Huo D, Ishikawa A, Peabody TD, He TC, et al . Myoid differentiation and prognosis in adult pleomorphic sarcomas of the extremity: An analysis of 92 cases. Cancer 2003;98;805-13.  Back to cited text no. 3    
4.Kempson RL, Kyriakos M. Fibroxanthosarcomas of the soft tissues: A type of malignant fibrous histiocytoma. Cancer 1972;29:961-76.  Back to cited text no. 4  [PUBMED]  
5.Weiss SW, Enzinger FM. Malignant fibrous histiocytoma: An analysis of 200 cases. Cancer 1978;41:2250-66.  Back to cited text no. 5  [PUBMED]  
6.Weiss SW. Malignant fibrous histiocytoma: A reaffirmation. Am J Surg Pathol 1982;6:773-84.  Back to cited text no. 6  [PUBMED]  
7.Fletcher CD. Pleomorphic malignant fibrous histiocytoma: Fact or fiction? A critical reappraisal of 159 tumors diagnosed as pleomorphic sarcomas. Am J Surg Pathol 1992;16:213-28.  Back to cited text no. 7    
8.Fletcher CD, Unni KK, Mertens F, editors. World Health Organisation classification of tumors: Pathology and genetics of tumors of soft tissue and bone. Lyon: IARC Press; 2002.  Back to cited text no. 8    
9.Segal NH, Pavlidis P, Antonescu CR, Maki RG, Noble WS, DeSantis D, et al . Classification and subtype prediction of adult soft tissue sarcomas by functional genomics. Am J Surg Pathol 2003;163:691-700.  Back to cited text no. 9    
10.Fletcher CD. The evolving classification of soft tissue tumors: an update based on the new WHO classification. Histopathology 2006;48:3-12.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]
11.Gaffney EF, Dervan PA, Fletcher CD. Pleomorphic rhabdomyosarcoma in adulthood: Analysis of 11 cases with definition of diagnostic criteria. Am J Surg Pathol 1993;17:601-9.  Back to cited text no. 11  [PUBMED]  
12.Furlong MA, Mentzel T, Fanburg-Smith JC. Pleomorphic rhabdomyosarcoma in adults: A clinicopathologic study of 38 cases with emphasis on morphologic variants and recent skeletal muscle specific markers. Mod Pathol 2001;14:595-603.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Gebhard S, Coindre JM, Michels JJ, Terrier P, Bertrand G, Trassard M, et al . Pleomorphic liposarcoma: clinicopathologic, immunohistochemical and follow-up analysis of 63 cases: A study from French Federation of Cancer Centers Sarcoma Group. Am J Surg Pathol 2002;26:601-16.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.Hornick JL, Bosenberg MW, Mentzel T, McMenamin ME, Oliveira AM, Fletcher CD. Pleomorphic liposarcoma: Clinicopathologic analysis of 57 cases. Am J Surg Pathol 2004;28:1257-67.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]

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Correspondence Address:
Manjula Jain
Department of Pathology, Lady Hardinge Medical College, New Delhi - 110 001
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9371.44040

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    Tables

  [Table 1], [Table 2], [Table 3]

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    Introduction
    Diagnostic Approach
    Salient Clinicop...
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