Soft tissue tumors - Histopathological study of 93 cases

Objective: Histopathological and immunohistochemical examination of soft tissue tumors to assess the value of these techniques in verifying the primary diagnosis and their classification. Methods: A prospective study of 93 consecutive soft tissue biopsies that reached the department of histopathology, central labs, Dohuk, and application of immunohistochemical markers on 27 biopsies. Results: Out of 93 soft tissue tumors, 70 (75.2%) were benign with mean age 27.6 y. and 23 cases (24.8 %) were malignant with mean age 39.1 y.. Immunohistochemistery was performed in 27 cases; 21 (77.7%) cases of malignant tumors and 6 (22.3%) benign cases. The most common benign tumors were Lipoma, Haemangioma, Neurofibroma, while malignant muscle tumors (leiomyosarcoma and Rhabdomyosarcoma) and malignant round cell tumors (Ewing’s sarcoma/ PNET) were the major groups . Conclusion: High quality H and E stained section, remain the best method for establishing the primary diagnosis of soft tissue tumors, but immunohistochemical examination proved extremely helpful in sub classifying them, where 7 out of 9 cases of gastrointestinal tumors (GISTs) showed strong immunoreactivity with (c – kit proteins) CD117, CD34 , while other (non GISTs) tumors were negative.

oft tissue tumors (STTs) are defined as mesenchymal proliferations that arise in the extra skeletal nonepithelial tissue of the body exclusive of the viscera, coverings of the brain and lymphoreticular system (1) .STTs are classified according to the tissue that they recapitulate or principally based on line of differentiation of tumors, rather than the type of tissue from which they developed.They include tumors of voluntary muscle, fat, fibrous S tissues, tumors of vessels serving them and peripheral nervous tissues.However, in some STTs, no corresponding normal counterpart is known (2) .
Soft tissue tumors (STTs) are infrequent neoplasms with the exception of skeletal neoplasms, However, benign tumors outnumber their malignant counterpart at least 100:1 due to their rarity as well as the variation and frequent overlap in their histopathological features, accurate diagnosis of STTs is a constant challenge to pathologists (2,3) .
Soft tissue tumors (STTs) usually affects old persons as about 40% of the affected are 55 years old or older and only 15% are younger than 15 years (2) .Certain prognostic factors for (STTs) should be taken in consideration in order to predict the outcome of tumor which include the age at presentation, size and site of the tumors, tumors' grade and histological subtype (5,6) , and factors associated with poor prognosis including old patient (> 60 years) tumor size (>5 cm) and high grade histology with deep seated tumors (7) .
Aims of the study 1.To assess the relative frequency of soft tissue tumors.2. To assess the role of immunohistochemical markers in the primary diagnosis and subclassification of soft tissue tumors.

Materials and methods
During a period of one year (from 2007 -2008)

Result
During a period of one year, 93 cases of soft tissue tumors were collected.There were (70) cases 75.2 % of benign soft tissue tumors with mean age of 27.6 y. and ( 23) cases (24.8 %) malignant one with mean age of 39.1 y. (table 2)..
Although clinical regarding age, site, size of the lesions are critical for the diagnosis of STTs, but histological examination remains the cornerstone for their diagnosis.However, certain complementary methods like EM and immnunohistochemical examination (IHC) may be needed to confirm the diagnosis and to establish their classification (9) .The IHC should be applied after careful H & E examination in order to limits the number of markers selected in every specific case.In this study many markers were applied for confirmation of diagnosis.
Vimentin is the most known broad spectrum marker for detection of mesenchymal tumors.It is an intermediate filament protein where the desmin and cytokeratin belong to this group of cytoskeleton.In general vimentin reacts with fibroblasts, Endothelial cells and smooth muscle of leiomyoma of the uterus (but not with that arising in the gastrointestinal tract) (10,11) .This wide variation in immunoreactivity of vimentin makes it of limited diagnostic value.In this study many benign and malignant tumors were positive for vimentin (table 4).Due to the lack of specific markers for fibrohistiocytic tumors, Vimentin is known as the only marker positive in fibrohistiocytic tumors, that is why the diagnosis of these tumors is based on the absence of markers of other lineages (12) .In this study there were two cases of MFH showing strong immunoreactivity for vimentin.
S-100 protein is widely distributed in peripheral (Schwann cells) and central nervous system (Astrocytes and oligodendrocytes) as well as melanocytes indicates that these cells are both considered to arise from neural crest, the result of this study confirms this correlation (13) , but it is also appeared in other tumor that does not show neuronal differentiation like glomus tumor (table 4) .Actin is a marker which is expressed in tumors that arise from striated and smooth muscle fibers like leiomyoma, rhabdomyoma, rhabdomyosarcoma and leiomyosarcoma as well as few types of vascular tumors like glomus tumor and hemangiopericytoma; these contractile proteins are classified as alpha (skeletal, cardiac and smooth muscle) and beta (cytoplasmic) and gamma (smooth muscle and cytoplasmic) (14) .In this study actin was positive with the above mentioned tumors except for rhabdomyosarcoma because we use smooth muscle actin where the specificity of smooth muscle actin is more restricted (it doesn't detect skeletal and cardiac muscle actin).These results were compatible with others (15)(16) .Desmin is intermediate filament markers for skeletal, cardiac and smooth muscle; it is expressed in 95 % of Rhabdomyosarcoma and variable smooth muscle tumor Fig. (1 A, B ).Other tumors may share this reactivity like MFH (17) , this expression of conventional markers of muscle fiber tumors in some cases of MFH may raise the questions about the nature of this tumor and its histogenesis.
Myxoid liposarcoma in this study was negative for all markers, although few cases of liposarcomas express focal reactivity for S-100 protein (20) ; a finding compatible with others Fig ( 2 A, B ).
Gastrointestinal stromal tumors (GISTs) comprise the largest subset of mesenchymal tumors of the gastrointestinal tract, they are characterized by expression of tyrosine kinase growth factor receptors (c-Kit antigen).These neoplasms differ immunohistologically and behaviorally from other mesenchymal tumors such as leiomyosarcoma which does not express Kit antigen.Most GISTs express CD 34 and CD 117 (c-kit protein) but not desmin (21) .In the current study there were 9 cases of GISTs (8 malignant and one benign), 7 cases were positive for CD 117 and CD 34 , which was compatible with others (22) .
Both cell surface antigen P30/ 32 (CD 99 ) and NSE are markers of tumors that express a neural differentiation (23) .These include Ewing's sarcoma of bone and soft tissue (Fig. 3) and primitive neuroectodermal tumor (PNET) where molecular studies have recently revealed that (PNET) and Ewing's sarcoma entities that once considered unrelated, are perhaps best considered as members of the same family (24,25) .In this study there were 5 cases all were positive for these markers, a result matched with other studies (26) .
In this study the malignant tumors constitute about quarter of all STTs, and this result does not reflect the accurate incidence of malignant tumors, because not all benign tumors are excised and rarely sent for histopathological examination.
Finally the IHC is a good tool in the differentiation between large numbers of soft tissue tumors and it is an indispensable procedure for the solution of the diagnostic challenges facing the pathologist.

Figure ( 1
Figure (1-A): Leiomyosarcoma.This tumor consists of elongated cells with a cigarshaped nucleus and eosinophilic cytoplasm, with several mitosis.

Figure ( 3
Figure (3): Ewing's sarcoma (H and E stain) sheets of small round cells slightly larger than lymphocytes.

Table ( 1
): Markers most commonly used to correlate with histogenesis.The immunostaining was used in 27 cases depending on the differential diagnosis which was highlighted by H & E staining where 7 cases of gastrointestinal stromal tumors out of 9 cases show positive immunoreactivity for CD 117 , CD 34 ((c -kit proteins)) (table4).

Table ( 2
): Type and number of soft tissue tumors with mean age.
Conclusion1.H and E stained sections remain the best method for establishing the primary diagnosis of soft tissue tumors.2. Immunohistochemistry is of great help in accurate categorization of both benign and malignant tumors particularly (c-kit protein) CD 117 , CD 34 in GISTs .