Dear Editor

We appreciated the comments of Dr Zardawi [1] and agree that actin is a ubiquitous cytoskeletal protein of microfilaments and demonstrable in a variety of cells and tumor types. As we described, all leiomyosarcomas are smooth muscle actin (SMA)-positive, and desmin, muscle specific actin (MSA) and h-caldesmon are positive in a great majority of these tumors. However, none of these is absolutely specific for smooth muscle, and positivity for two or more of these markers is more supportive of leiomyosarcoma than positivity for one alone.

Anti-SMA monoclonal antibody, 1A4, detects mainly with an alpha smooth muscle actin isoform. This marker exhibits a more restricted pattern of staining for smooth muscle, but this may be expressed in rhabdomyosarcomas and in cells with a myofibroblastic or myoepithelial phenotype. As another anti-MSA monoclonal antibody, HHF35, recognizes all alpha actins (skeletal, smooth, and cardiac) and gamma smooth muscle actin, its specificity for smooth muscle is therefore quite limited. In this regard, recognition of the fact that non-muscle lesions exhibiting so-called myoid differentiation are also SMA-positive will prevent overdiagnosis as leiomyosarcoma.

Reference

(1) Zardawi IM. Re: Expression of smooth muscle markers in so called malignant fibrous histiocytoma [electronic response to Hasegawa et al Expression of smooth muscle markers in so called malignant fibrous histiocytomas] jclinpath.com 2003http://jcp.bmjjournals.com/cgi/eletters/56/9/666#45

Dear Editor

I read with interest the article on the expression of smooth muscle markers in so called malignant fibrous histiocytomas by Hasegawa et al. in the Journal.[1]

While I agree with Hasegawa and colleagues that pleomorphic malignant fibrous histiocytoma can be regarded as an undifferentiated sarcoma, I feel Hasegawa et al are placing too much reliance on so called smooth muscle markers. Most of these markers are ubiquitous, present in many cells. Many of the so called muscle specific markers stain microfilaments which form the cytoskeletal framework of most cells. However, these markers are particularly expressed in muscle cells, myoepithelial cells cell and myofibroblasts. In neoplasia, these markers indicate myogenic differentiation which can be seen in a raft of tumours which make them unreliable in tumour classification.

A search of the Internet (www.ipox.org) shows smooth muscle actin (SMA) immunoreactivity in 150 types of tumour from different parts of the body with 100% staining in 32 tumour types, between 50% and 99% staining in 45 tumour types, and between 4% and 49% staining in 73 tumour types. The same source cites 0% staining in 80 tumour types. The question that needs to be asked therefore is not which tumours are SMA positive but rather which tumours do not express this marker.

SMA is very much like neuron specific enolase (NSE) which can be found in neurons, neuroendocrine cells, striated and smooth muscle cells, megakaryocytes, T cells and platelets to name a few. NSE reactivity has been reported in over 140 tumour types (www.ipox.org).

Reference

(1) Hasegawa T, Hasegawa F, Hirose T, Sano T, Mastuno Y. Expression of smooth muscle markers in so called malignant fibrous histiocytoma. J Clin Pathol 2003; 56:666-671.