Desmin‐positivity in spindle cells: Under‐recognized immunophenotype of lipoblastoma

Lipoblastoma is a distinct benign fatty tumor composed of adipocytes, lipoblasts, and primitive mesenchymal cells with a myxoid stroma. Lipoblastoma harbors characteristic fusion genes involving the PLAG1, resulting in aberrant expression of PLAG1. However, the nature of the primitive mesenchymal cells remains obscure. In our routine pathology practice, we noticed desmin‐positive spindle mesenchymal cells in lipoblastomas, which is a hitherto poorly described phenomenon. Thus, we examined the expression of several myogenic markers including desmin in a variety of 95 mesenchymal tumors with fatty elements. Fourteen of the 15 lipoblastomas examined contained desmin‐positive spindle cells, which also showed nuclear expression of PLAG1, whereas α‐smooth muscle actin, muscle specific actin, h‐caldesmon, and myogenin were negative. Some spindle cells in subsets of atypical lipomatous tumors/well differentiated liposarcomas (6/20), dedifferentiated liposarcomas (11/31) and pleomorphic liposarcomas (2/10) were positive for actins and/or desmin, supporting focal myofibroblastic or smooth muscle differentiation. The other tumors, including 11 myxoid/round cell liposarcomas, four spindle cell lipomas, and four lipofibromatoses, were negative for all of the myogenic markers assessed. The almost consistent desmin expression in spindle mesenchymal cells suggests a potential diagnostic utility of this marker and myofibroblastic phenotype of fractions in lipoblastoma cells.     

Immunophenotypic diagnosis of leiomyosarcomas and rhabdomyosarcomas with monoclonal antibodies to muscle-specific actin and desmin in formalin-fixed tissue

Two fibrillary proteins, muscle-specific actin (MSA) and desmin, are found only in cells of smooth and skeletal muscle lineages. Among the monoclonal antibodies (MAbs) to these antigens which we have tested, we found several to be reactive in formalin-fixed, paraffin-embedded sections. This finding widened the possibility of using these MAbs in routine diagnostic surgical pathology for the immunodiagnosis of rhabdomyosarcomas (RMS) and leiomyosarcomas (LMS). We therefore conducted a comparative study of three such MAbs which are available commercially and which we applied to paraffin-embedded, formalin-fixed tissues from 15 patients with RMS and 19 patients with LMS. The case selection criteria included typical light-microscopic appearances as well as immunoreactivity with at least one of the MAbs. MSA was detected in all cases of RMS and LMS, whereas desmin was reactive in 12 of 13 RMS and 10 of the 19 LMS. (Desmin antigenicity was judged to be lost in two RMS, since the vascular smooth-muscle tissue present in the specimens failed to react with these antibodies.) In LMS, desmin tended to show focal positivity, whereas the MSA in the same specimens was diffusely positive. These results demonstrate the utility of MAbs for confirmation of the muscle lineage of LMS and RMS in formalin-fixed, paraffin-embedded tissue. The results also indicate that, with the MAbs tested, the antigenicity of MSA is preserved more consistently than that of desmin in formalin-fixed, paraffin-embedded tissue, and that MSA is a more sensitive marker for the detection of muscle differentiation than is desmin, especially in LMS.     

MED12 mutations occurring in benign and malignant mammalian smooth muscle tumors

Mutations of the mediator subcomplex 12 gene (MED12) recently have been described in a large group of uterine leiomyomas (UL) but only in a single malignant uterine smooth muscle tumor. To further address the occurrence of fibroid‐type MED12 mutations in smooth muscle tumors, we have analyzed samples from 34 leiomyosarcomas (LMS), 21 UL, two extrauterine leiomyomas (EL), and 10 canine genital leiomyomas for the presence of MED12 mutations of the UL‐type. Interestingly, besides UL MED12 mutations were found in one uterine LMS, one EL, and two canine vaginal leiomyomas. The results confirm the occurrence of fibroid‐type MED12 mutations in malignant uterine smooth muscle tumors thus suggesting a rare but existing leiomyoma‐LMS sequence. In addition, for the first time MED12 mutations are reported in smooth muscle tumors in a non‐primate mammalian species. © 2012 Wiley Periodicals, Inc.     

An immunohistochemical and clinicopathological study of gastrointestinal stromal tumors

Immunohistochemical and clinicopathological features of 58 gastrointestinal stromal tumors (GIST) were studied. One occurred in the esophagus, 41 in the stomach, nine in the small intestine, and seven in the large intestine. By using indirect immunoperoxidase staining for Cajal cell markers (c-kit protein and CD34), smooth muscle markers (alpha-smooth muscle actin, desmin, heavy caldesmon and calponin) and Schwann cell markers (S-100 protein and Leu 7), GIST were classified into five groups, such as Cajal cell type (n = 9), myogenic type (n = 5), Schwann cell type (n = 2), mixed cell type (n = 40) and undifferentiated type (n = 2). c-kit Protein (42/58; 72%) and CD34 (45/58; 78%) were commonly and diffusely expressed in GIST. Novel smooth muscle markers, caldesmon (29/58; 50%) and calponin (18/58; 31%), were useful in detecting myogenic characters of GIST. S-100 protein was expressed in 16 (28%) tumors, two of which were also reactive with Leu 7 (CD57). Three small bowel tumors with skeinoid fibers expressed the Cajal cell markers, and were categorizable in GIST. Clinicopathological analyses using aggressive (n = 21) and non-aggressive (n = 21) GIST indicated that the malignant potential was correlated with the intestinal location, large tumor size, high cellularity, necrosis, solid (non-interlacing bundled) pattern of growth, negativity of c-kit protein and/or CD34, high mitotic count, and high MIB-1 labeling.     

Comparative immunohistochemical staining for desmin and muscle-specific actin. A study of 576 cases.

Muscle-specific actin (MSA) and desmin are considered to be sensitive and specific markers for muscle differentiation. The authors compared staining patterns for these markers in 576 samples of normal, reactive, and neoplastic tissues. The standard avidin-biotin-peroxidase complex technique was performed with the use of two commercial antibodies against MSA (HHF35; Enzo Biochemical, Inc., New York, NY) and desmin (DER11; DAKO Corporation, Santa Barbara, CA), respectively, on consecutive paraffin-embedded tissue sections from these cases. Both MSA and desmin were found in all 80 normal muscle samples. Although MSA appeared diffusely in all vascular smooth muscle samples, desmin was demonstrated focally in vascular smooth muscle cells in 100 of 196 samples. MSA but not desmin always was found in myoepithelial cells (25 samples), pericytes (286 samples), and decidual cells (7 samples). Among 76 cases of myofibroblast-containing lesions, 14 and 54 were found to have desmin and MSA, respectively. MSA and desmin were found in 4 of 4 cardiac rhabdomyomas, 34 of 34 rhabdomyosarcomas, and 5 of 6 leiomyomas. Among 22 leiomyosarcomas, 7 displayed either MSA or desmin and 7 showed both markers. In general, more tumor cells showed staining for MSA than desmin, but the reverse was true in some cases. Tissue fixed in Zenker's solution seemed to show a significant decrease in MSA immunoreactivity, but no significant change for desmin staining was observed. None of the 154 normal tissues and 22 benign nonmyogenic tumors expressed MSA or desmin. Among 133 malignant nonmyogenic tumors, positive staining for both desmin and MSA was found in 3 of 8 cases of glioblastoma multiforme, 1 of 10 malignant schwannomas, and 1 of 14 malignant fibrous histiocytomas; staining for only MSA was found in 3 of 14 malignant fibrous histiocytomas, 1 of 10 malignant schwannomas, 6 of 6 fibromatoses, 1 of 1 mammary myofibroblastoma, and 1 of 7 malignant mesotheliomas; and staining for desmin only was seen in 1 of 7 malignant mesotheliomas.(ABSTRACT TRUNCATED AT 400 WORDS)     

Leiomyosarcoma of somatic soft tissues in childhood: an immunohistochemical analysis of six cases with ultrastructural correlation

Leiomyosarcoma (LMS) of soft tissue is a rare tumor in children. Although LMS may exhibit clinical and histologic features that are typical of smooth muscle neoplasms in adults, they may often be confused with or resemble tumors of presumed fibroblastic, myofibroblastic, or rhabdomyoblastic differentiation. As a result, the diagnosis of LMS in children is often difficult to establish with confidence. To address this problem, we analyzed the immunohistochemical features of six LMS in children (one of deep soft tissue of an extremity, one of paravertebral tissue, one of the retroperitoneum, two of oropharyngeal soft tissue, and one of subcutis); the ultrastructural features of four of these tumors were also studied. Histologically, each of the three tumors of deep soft tissue and one of the retromolar trigone were composed of pleomorphic spindle cells arranged in interweaving fascicles. In contrast, the subcutaneous tumor and the lesion of the hard palate had an epithelioid appearance. Ultrastructural features were typical of adult type LMS. Immunohistochemically, these neoplasms were diffusely reactive for vimentin, while each was negative for cytokeratin, epithelial membrane antigen, and S-100 protein. Desmin was present in all cases, but was expressed only focally in three; a similar pattern of staining was noted for muscle-specific actin, although staining was generally noted in a larger population of cells. alpha-1-Antichymotrypsin was found in five tumors, and cathepsin B reactivity was encountered in four cases. Leu-7 antigen and myelin basic protein were coexpressed by one tumor, but neither was found in the remaining cases. These results indicate that immunohistochemical detection of desmin and muscle-specific actin may be useful in the differential diagnosis of spindle or epithelioid cell proliferations in childhood when ultrastructural analysis in unavailable.     

Intermediate and fine filaments of vascular leiomyomas (angiomyoma), leiomyoma and leiomyosarcomas of large veins

The expression of fine and intermediate filaments in 10 cases of leiomyosarcoma originating from a large vein, 9 cases of vascular leiomyoma (angiomyoma) and one case of a leiomyoma originating from the wall of the saphena magna vein was studied immunohistochemically by using 6 different anti-desmin antibodies, one anti-vimentin antibody and 2 antibodies to muscle-specific isoforms of actin. All the benign tumors and all the leiomyosarcomas of a large vein as well as the vein of origin were positively stained for desmin. The staining results obtained using the different anti-desmin antibodies varied considerably, however, and formaldehyde-fixed tissues were apparently inappropriate for some of them. No single anti-desmin antibody produced a positivity in all cases, and the extent and distribution of the positivity varied by being irregular and patchy in the leiomyosarcomas and in the muscle walls of the veins, while the benign tumors generally revealed a more uniform and strong positivity. Antibodies to muscle-specific and smooth muscle-specific actin produced a positive staining in all the benign tumors, as well as all the leiomyosarcomas and the veins from which they originated. A strong and uniform positivity was observed in the benign tumors and muscle walls of the veins, while the positivity in the leiomyosarcomas was more irregular, as it was for desmin. Vimentin was constantly expressed in the benign tumors and in the veins of origin, but only in 5/10 of the leiomyosarcomas. It is concluded from this study that the immunohistochemical demonstration of desmin, utilizing a monoclonal antibody appropriate to the type of fixation used, and muscle specific isoforms of actin, provide strong support to the light-microscopic diagnosis of leiomyosarcoma of venous origin.     

High‐grade endometrial stromal sarcoma with smooth muscle and skeletal muscle differentiation: Report of a case with cytomorphologic and immunocytologic analysis

We report a case of high‐grade endometrial stromal sarcoma with cytological and immunocytochemical findings. Cytologically, major tumor cells showed round‐to‐short spindle shapes with round‐ to oval‐shaped nuclei and moderately abundant delicate cytoplasm. Tumor cells with tapered shapes and eccentric nuclei were also observed. A few spindle cells having enlarged cigar‐shaped nuclei with conspicuous nucleoli and delicate wispy cytoplasm, which resembled leiomyosarcoma, were intermingled. One rhabdomyoblast cell with both α‐sarcomeric muscle actin and myoglobin was also observed. Most of the tumor cells, including the leiomyosarcomatous spindle cells, were positive for CD10, and negative for desmin and h‐caldesmon. Accordingly, when relatively monotonous round‐to‐short spindle tumor cells and taper‐shaped tumor cells are observed in the female genital tract, high‐grade endometrial stromal sarcoma should be considered in the differential diagnosis. Immunocytochemistry contributed to the correct diagnosis. This case was high‐grade endometrial stromal sarcoma with smooth muscle and skeletal muscle differentiation. Diagn. Cytopathol. 2010. © 2010 Wiley‐Liss, Inc.     

Pleomorphic sarcoma as a mimicker of sarcomatous carcinoma

The fourth case of a poorly differentiated sarcoma histologically mimicking a sarcomatous carcinoma is reported. The tumor was focally weakly positive for keratin, moderately focally positive for epithelial membrane antigen, muscle-specific actin, smooth muscle actin, and calponin, and strongly diffusely positive for vimentin. The neoplastic cells were closely apposed, often without intervening intercellular matrix; the cell membranes were straight and contained desmosome-like junctions. The cytoplasm contained a moderate number of mitochondria, rough endoplasmic reticulum, ribosomes, and many vesicles. The karyotype was complex and many chromosomal rearrangements were present. The diagnostic term carcinomatoid sarcoma is proposed for these interesting, insufficiently studies, tumors.     

Pleomorphic Sarcoma as a Mimicker of Sarcomatous Carcinoma

The fourth case of a poorly differentiated sarcoma histologically mimicking a sarcomatous carcinoma is reported. The tumor was focally weakly positive for keratin, moderately focally positive for epithelial membrane antigen, muscle-specific actin, smooth muscle actin, and calponin, and strongly diffusely positive for vimentin. The neoplastic cells were closely apposed, often without intervening intercellular matrix; the cell membranes were straight and contained desmosome-like junctions. The cytoplasm contained a moderate number of mitochondria, rough endoplasmic reticulum, ribosomes, and many vesicles. The karyotype was complex and many chromosomal rearrangements were present. The diagnostic term carcinomatoid sarcoma is proposed for these interesting, insufficiently studies, tumors.     

Cell markers in gastrointestinal stromal tumors

Stromal tumors of the gastrointestinal (GI) tract have generated considerable controversy about their direction and level of differentiation, particularly about whether the tumor cells are smooth muscle or Schwann cells. In an attempt to characterize these tumors, the immunohistochemical staining patterns of desmin, vimentin, actin, and S-100 protein were studied in 41 GI stromal tumors, using the avidin-biotin method, and compared with normal host smooth muscle and nerve and with esophageal and uterine leiomyomas. Twenty gastric and one rectal tumor stained diffusely with vimentin and actin, but not with desmin, and had scattered strongly S-100-positive cells that might either be trapped Schwann cells or tumor cells. Twenty small bowel tumors stained similarly to the gastric tumors with regard to vimentin, actin, and desmin, but most (17/20) had a unique, strongly positive geographic staining pattern with S-100. No differences in staining were noted between benign and malignant tumors in either gastric or small bowel sites, and most histologic patterns in tumors from similar locations stained similarly. These results suggest that GI stromal tumors are not truly "leiomyomas and leiomyosarcomas," but relatively undifferentiated tumors, with the expression of various antigens depending on their location in the gut.     

Intravascular myopericytoma: an interesting case of a long-standing large, painful subcutaneous tumor

Myopericytoma is a benign neoplasm consisting of cells that appear to have a distinct differentiation towards presumed perivascular myoid cells. Amongst myopericytoma, an intravascular variant appears to have been reported only rarely. A 67-year-old man presented with a 15-year history of a painful, slow growing 3 × 3.5 cm sized mass in the subcutis of his right lateral thigh. Histopathological studies showed a subcutaneous mass entirely within the lumen of a vein. The tumor was composed of spindle-shaped myoid-appearing cells in a concentric arrangement, intimately associated with thin-walled vascular channels. Tumor cells were diffusely positive for smooth muscle actin, focally positive for CD34, and negative for desmin and CD31. From these findings, we diagnosed this lesion as intravascular myopericytoma. Unlike previous reports, our case showed a relatively large painful subcutaneous mass, although this tumor has an intravascular nature.     

The intermediate filament proteins of rabbit vascular smooth muscle: immunofluorescent studies of desmin and vimentin

Summary The localization of desmin and vimentin in rabbit vascular smooth muscle was studied using the fluorescent antibody technique. Desmin and vimentin were present in the smooth muscle cells of the portal anterior mesenteric vein, renal vein and renal artery. All endothelial cells and the smooth muscle cells of the abdominal aorta and main pulmonary artery contained only vimentin. The results suggest that desmin and vimentin are differentially distributed in rabbit vascular smooth muscle and that both may occur in a single blood vessel.     

Myoid gonadal stromal tumor: a distinct testicular tumor with peritubular myoid cell differentiation

We report a distinct, primary testicular tumor with peritubular myoid cell differentiation. A 25-year-old man developed a well-circumscribed testicular tumor composed of cytologically bland spindled cells, which were strongly and diffusely positive for desmin, smooth muscle actin, muscle-specific actin, and smooth muscle myosin. In addition, S-100 was diffusely positive, and cytokeratin (CK5/6 and AE1/3) was focally positive. Calretinin, inhibin, and CD34 were all negative. This pattern of immunoreactivity was very similar to the normal adjacent peritubular myoid cells. Follow-up after radical orchiectomy showed benign behavior. We found reports of 6 similar intratesticular tumors demonstrating peritubular myoid cell-like differentiation and having favorable outcome. We believe that the myoid gonadal stromal tumor is a rare, yet distinct, testicular tumor separate from leiomyoma and deserves recognition.     

Myoepithelial differentiation markers in salivary gland neoplasia]

Salivary gland tumors frequently present myoepithelial cell differentiation that is not always easily identified on routinely stained sections. Recently novel markers of myoepithelium have been studied, such as calponin (CALP), caldesmon (CALD), and smooth muscle myosin heavy chain. These markers, together with smooth muscle actin may be useful tools for identifying myoepithelial cells. We immunohistochemically studied a series of 23 benign and malignant salivary gland tumors using antibodies to these four markers. The tumors were classified as follows: pleomorphic adenoma (n = 8), basal cell adenoma (n = 3), myoepithelioma with plasmacytoid cells (n = 2), epithelial-myoepithelial cell carcinoma (n = 6) and adenoid cystic carcinoma (n = 4). All tumors were positive for at least one of the four markers. CALP and smooth muscle actin were the markers more frequently expressed. Positivity was mostly located in the myoepithelial cells that constitute the external layer of the glandular or tubular neoplastic structures. In poorly differentiated epithelial myoepithelial carcinomas, composed of solid sheets of neoplastic cells and sometimes of clear cells, immunohistochemical staining for myoepithelial markers evidenced rudimentary glandular structures. CALP and smooth muscle actin were positive in the two cases of myoepithelioma with plasmacytoid cells. In conclusion, the combined staining with four markers helps to disclose myoepithelial cell differentiation and can be a useful tool for the correct histopathological diagnosis of salivary gland tumors. Among the four markers studied, CALP and smooth muscle actin were the most useful to identify myoepithelial cell differentiation.     

Intermediate filament proteins and actin isoforms as markers for soft-tissue tumor differentiation and origin. III. Hemangiopericytomas and glomus tumors.

Intermediate filament proteins and actin isoforms of a series of 12 malignant hemangiopericytomas and five glomus tumors were examined by light microscopy, transmission electron microscopy, two-dimensional gel electrophoresis (2D-GE), and by immunohistochemistry, the latter using monoclonal or affinity-purified polyclonal antibodies to desmin, vimentin, cytokeratins, alpha-smooth muscle, and alpha-sarcomeric actins. By light microscopy, all hemangiopericytomas disclosed a predominant vascular pattern with scant storiform, myxoid and spindle cell areas, and with variable degrees of perivascular fibrosis. By ultrastructure, smooth muscle differentiation was observed in each hemangiopericytoma. Immunohistochemically, neoplastic cells of hemangiopericytomas expressed vimentin as the sole intermediate filament protein and lacked alpha-smooth muscle or alpha-sarcomeric actins. 2D-GE revealed only beta and gamma actins, in proportions typical for fibroblastic tissues. Glomus tumors revealed vimentin and alpha-smooth muscle actin within glomus cells by immunohistochemical techniques and disclosed ultrastructurally distinct smooth muscle differentiation. Therefore hemangiopericytomas represent a distinct soft-tissue neoplasm with uniform morphologic, immunohistochemical, and biochemical features most likely related to glomus tumors, the former representing an aggressive and potentially malignant neoplasm of vascular smooth muscle cells and the latter a well-differentiated neoplasm of vascular smooth muscle cells. Because malignant hemangiopericytomas disclose smooth muscle differentiation by ultrastructure, but do not express alpha-smooth muscle actin, as normal pericytes and glomus cells, it is suggested that these neoplasms represent highly vascularized smooth muscle neoplasms, ie, poorly differentiated leiomyosarcomas derived from vascular smooth muscle cells or their equivalent, the pericytes, which have lost alpha-smooth muscle actin as a differentiation marker that is similar to many conventional poorly differentiated leiomyosarcomas.     

Expression of intermediate filaments in malignant fibrous histiocytomas

The expression of intermediate filaments (IFs) in 34 malignant fibrous histiocytomas (MFHs) was studied immunohistochemically and ultrastructurally. Using the avidin-biotin-peroxidase method, positive reactions were detected as follows: for desmin in 12 tumors, for neurofilament in two tumors, for cytokeratin in one tumor, and for vimentin in 30 tumors. Desmin immunoreactivity was found in tumors of all four histologic subtypes and cytokeratin immunoreactivity was found in one tumor of the myxoid type. Because of the cross-reactivity of anti-neurofilament antibody with reactive histiocytes, the immunoreactivity for neurofilament seemed to be non-specific. Ultrastructurally, five of 13 tumors studied contained some tumor cells showing myofibroblastic or smooth muscle cell differentiation. A few tumor cells in one cytokeratin-positive tumor had tonofilaments in their cytoplasm. Desmin expression in some MFHs seemed to be due to myofibroblastic or smooth muscle cell differentiation of some tumor cells. Cytokeratin expression seemed to indicate epithelial differentiation in some MFHs. This varied expression of IFs in MFHs may reflect the heterogeneous nature of MFHs, and suggests that MFHs represent the final stages of dedifferentiation of several different types of sarcomas or, alternatively, represent forms of poorly differentiated sarcoma with the potential of developing into more differentiated sarcomas of heterogeneous origin.     

Myxoid mesenchymal tumors of uterus: endometrial stromal and smooth muscle tumors, myxoid variant

Four myxoid variant of uterine mesenchymal tumors are reported. One was a low grade stromal sarcoma with infiltrative margins and the others were well circumscribed tumors corresponding to an endometrial stromal nodule and two leiomyomas. They were hypocellular neoplasms composed of stellated cells with an abundant Alcian Blue positive myxoid matrix. The myxoid nature of the neoplasms obscured their cellular nature and made the distinction between smooth muscle and endometrial stromal tumors difficult. Endometrial stromal tumors, showed very focal areas of small basophilic cells, characteristic of endometrial stroma. The diagnosis was based on the presence of a spiral arteriolar network, a CD10 positivity as well as the absence of h-caldesmon and desmin expression. The two myxoid leiomyomas showed more spindle cells and a desmin expression while h-caldesmon was negative and CD10 focally positive in both cases. Myxoid variant of endometrial stromal tumors does not necessarily exhibit the typical morphology of endometrial stroma. They may demonstrate morphological features of smooth muscle tumors in the uterus. Also, myxoid changes in uterin smooth muscle tumors may modify the classical immunoreactivity of smooth muscle markers in these tumors and make it difficult to distinguish between benign and malignant neoplasms. An immunohistochemical panel of antibodies including CD10, h-caldesmon and desmin may help in establishing the correct diagnosis.     

Induction of smooth muscle cells in the fibrous capsule of human hepatocellular carcinoma but not in the septa of hepatic cirrhosis

 We examined the expression of smooth muscle cytoskeleton in spindle-shaped cells in the capsule of hepatocellular carcinoma (HCC) and the septa of liver cirrhosis (LC). Serial sections of livers resected from 11 patients were stained with monoclonal antibodies against vimentin, desmin, smooth muscle actin (1A4, HHF35, CGA7) and smooth muscle myosin heavy chain isoforms (SM1, SM2). Capsular spindle-shaped cells exhibited a cytoskeletal feature indicative of intermediately differentiated smooth muscle cells. Computer-assisted morphometry revealed that the proportions of 1A4-, HHF35-, CGA7- and SM1- positive areas to vimentin-positive area were 88.0±11.0%, 50.8±17.4%, 25.3±16.4% and 19.4±12.4% (n=11) in main tumours and 86.6±9.4%, 50.9±18.7%, 21.1±12.3% and 17.6±9.7% (n=12) in daughter tumours, indicating that spindle-shaped cells are heterogeneous in cytoskeletal expression. Septal spindle-shaped cells in LC lacked the cytoskeletal proteins specific to differentiated smooth muscle cells (CGA7, SM1, SM2 and desmin). Electron microscopically, capsular spindle-shaped cells contained more microfilaments and less rough endoplasmic reticulum than do septal cells. Intermediately differentiated smooth muscle cells are induced in the capsule of HCC but not in the septa of LC, suggesting a role for stromal interaction by tumour cells in the induction of smooth muscle cells. Received: 23 July 1998 / Accepted: 20 December 1998