S-100 protein distribution in liposarcoma An immunoperoxidase study with special reference to the distinction of liposarcoma from myxoid malignant fibrous histiocytoma

The presence and distribution of S-100 protein were studied in 63 cases of liposarcoma and 20 cases of myxoid malignant fibrous histiocytoma (MFH), using the immunoperoxidase technique. Normal adipose tissue and benign lipomatous tumours were also studied by the same technique, for purposes of comparison. In all liposarcomas, most of the adipocytes and vacuolated lipoblasts were positive for S-100 protein, although the tumour cells in non-lipogenic areas of dedifferentiated liposarcoma and the non-vacuolated giant cells with a deeply eosinophilic cytoplasm in the pleomorphic liposarcomas were devoid of S-100 protein immunoreaction products. One third of the myxoid type liposarcomas contained numerous immunoreactive, immature-appearing spindle or oval cells, reminiscent of the primitive fat organs of white adipose tissue. Conversely, none of the myxoid MFHs contained S-100 protein in the tumour cells, including the irregularly vacuolated ones. These results suggests that the immunohistochemical demonstration of S-100 protein is a useful diagnostic tool, particularly for the assessment of vacuolated tumour cells and for the diagnosis of myxoid tumours.     

S-100 protein: Is it useful as a tumour marker in diagnostic immunocytochemistry?

A heterogeneous group of 159 tumours was studied for the presence of S-100 protein by the immunoperoxidase technique in order to determine whether this marker may be of value in facilitating immunocytochemical diagnosis. Among cases of melanocytic and pigmented lesions, S-100 was widely distributed and demonstrated the strongest degrees of reactivity. S-100 protein was identified in virtually all nerve sheath tumours such as schwannomas, neurofibromas, myxoid sheath nerve tumour and also in some tumours of controversial histogenesis such as granular cell tumours. The great majority of carcinomas did not express S-100, with only two cases of breast carcinoma displaying focal S-100 staining. In a miscellaneous group of tumours S-100 was demonstrated in chordomas, myoepitheliomas and Wilms' tumour with Schwann cell differentiation. Despite its presence in a wide array of cell types, S-100 protein continues to be an extremely useful marker especially for soft tissue and peripheral nervous system tumours.     

Extraskeletal myxoid chondrosarcomas do not show a chondrocytic phenotype.

Extraskeletal myxoid chondrosarcoma is a rare mesenchymal soft-tissue malignancy of putative chondrocytic differentiation. Occasional overt cartilage formation, positivity for S-100 protein, and ultrastructural analysis have supported this view. However, most extraskeletal myxoid chondrosarcomas do not show chondroid tissue formation, and S-100 protein is found much less commonly than has been reported. Both these observations cast doubt on the histogenetic classification of extraskeletal myxoid chondrosarcoma as a chondroblastic entity. Mostly using matrix proteins as markers of mesenchymal cell differentiation, we investigated the biochemical matrix composition and cellular phenotype of the tumor cells in representative specimens from 14 extraskeletal myxoid chondrosarcomas. In all but one tumor specimen, which showed histomorphologically overt cartilage formation, only occasional staining for the proteoglycan aggrecan was found. Specimens from two tumors showed presence of collagen type II, and none was positive for collagen type X. Instead, collagen types I, III, and VI were diffusely positive. Also, S-100 protein was largely absent. Our results suggest that the basic cellular phenotype of extraskeletal myxoid chondrosarcoma is not chondrocytic or prechondrocytic and that extraskeletal myxoid chondrosarcoma is not a chondrosarcomatous entity. Extraskeletal myxoid chondrosarcoma consists most likely of primitive mesenchymal cells with focal, multidirectional differentiation. Chondrocytic differentiation is an unusual facet in the spectrum of differentiation patterns exhibited by these lesions.     

Pleomorphic adenoma of the salivary gland in two dogs

Pleomorphic adenomas of the salivary gland were diagnosed in two dogs. The tumours were single, firm and well circumscribed, with a smooth cut surface. Metastatic tumours were not detected. Histopathological examination revealed that the tumours contained multiple cysts lined with luminal epithelial cells and myoepithelial cells, and mucinous, myxochondroid and cartilaginous tissues. Immunohistochemical examination demonstrated labelling of luminal epithelial cells and myoepithelial cells, and mucinous, myxochondroid and cartilaginous tissues with antibodies to cytokeratin LU-5, AE1/AE3, CK-14, CALP, a-SMA, vimentin, GFAP, and S-100. Labelling for GFAP indicated stromal transformation into myxoid and chondroid tissues.     

Clear cell malignant myoepithelioma of the salivary glands

Previous reports of monomorphic clear cell carcinoma of the salivary glands have shown inconsistent results with immunohistochemistry, especially for S-100 protein, and this has led to uncertainty about the nature of these tumours. We believe that much can be explained by considering this group as comprising not one but two separate neoplasms, one epithelial and the other myoepithelial. The former has been described as hyalinizing clear cell carcinoma—it generally occurs in the minor salivary glands, and strongly expresses cytokeratins but not S-100 protein or α smooth muscle actin. In contrast, this study presents five primary malignant tumours of the major salivary glands also composed largely of a single population of clear cells, but displaying histological and immunohistochemical features of myoepithelial differentiation, such as the formation of collagenous spherules and expression of S-100 protein and actin. A small number of similar tumours have been reported previously. We, therefore, believe that these neoplasms represent a clear cell variant of malignant myoepithelioma (myoepithelial carcinoma).     

Extraskeletal myxoid chondrosarcoma arising from the retroperitoneum

A case of extraskeletal myxoid chondrosarcoma is presented. The tumor occurred in the retroperitoneum and systemic metastases were found at autopsy. The primary and metastatic tumors were soft and strikingly myxoid on gross appearance. Microscopic observation revealed undifferentiated malignant tumor having large amounts of myxoid substance and a small amount of well-differentiated chondrosarcoma element in the primary lesions. The authors obtained an immunohistochemical result that the tumor cells showed positivity for alpha-1-antitrypsin and alpha-1-antichymotrypsin. Regarding S-100 protein, the well-differentiated chondrosarcoma element revealed intense positivity, whereas the poorly differentiated myxoid areas were not positive except for a few tumor cells. This is the first case, to our knowledge, of extraskeletal myxoid chondrosarcoma arising from the retroperitoneum, and immunohistologic findings suggest that alpha-1-antitrypsin and alpha-1-antichymotrypsin may be available markers in poorly differentiated chondrosarcomas showing a negative reaction for S-100 protein.     

Chordoma: an immunohistologic study

Fourteen chordomas, five myxoid chondrosarcomas, and 15 chondroid tumors (four mesenchymal and 11 conventional chondrosarcomas) were stained for cytokeratin, S-100 protein, carcinoembryonic antigen (CEA), and vimentin. The epithelial markers stained 93 per cent of the chordomas, whereas none of the tumors of other types showed any staining. Sixty-four per cent of the chordomas, 20 per cent of the myxoid chondrosarcomas, and 87 per cent of the other chondroid tumors were positive for S-100 protein. All of the tumors were positive for vimentin. Three of the 14 chordomas were positive for CEA. The present study confirms the utility of these markers in the differential diagnosis of chordoma and tumors with similar histologic characteristics.     

Application of markers in the diagnosis of soft tissue tumours

In this review we describe the application of markers which are useful for the diagnosis of soft tissue tumours in paraffin sections. Detection of intermediate filament proteins appears to be most useful for first screening of these neoplasms because all, except neuroblastomas, express vimentin; cytokeratin is expressed in synovial sarcomas, epithelioid sarcomas and mesotheliomas; desmin in myogenic tumours and glial fibrillary acidic protein in astrocytomas and gliomas. Tissue-specific markers are: factor VIII--related antigen-endothelial cells; myoglobulin and skeletal muscle myosin--skeletal muscle cells; neuron specific enolase--neurons and cells of the APUD systems; and leukocyte-associated antigen--leukocytes. Markers which are present in a variety of cell types and therefore do not serve as tissue-specific markers are; S-100 proteins, alpha-1-antichymotrypsin, creatine kinase M and actin. The S-100 antigens have been detected in melanomas, granular cell tumours, chondrosarcomas and in some schwannomas and liposarcomas. Alpha-1-antichymotrypsin has been found in fibrohistiocytic and 'true' histiocytic tumours and creatine kinase M and actin in myogenic tumours. No specific markers have, as yet, been described for fibrosarcomas, Ewing's sarcomas and hemangiopericytomas.     

Extraskeletal myxoid chondrosarcoma of the nasopharynx

Extraskeletal myxoid chondrosarcoma is a rare but distinct entity with special clinicopathological, immunohistochemical, cytogenetical and outcome features. This tumor developed from soft tissues. A few cases have been reported in the head and neck in the literature. We report two new cases of extraskeletal myxoid chrondrosarcoma presenting in such an unusual site: one involved the left nasal cavity of a 67-year-old man and the second the sphenoidal sinus of a 71-year-old woman. The microscopic examination revealed nests of round small cells dispersed in a myxoid stroma. The myxoid material was stained with Alcian Blue with and without hyaluronidase application whereas no PAS staining was observed. The immunohistochemical staining showed reactivity with S-100 protein and vimentin in two cases and with EMA in one case. These results allowed us to exclude other differential diagnoses: soft tissue tumors with a myxoid stroma (myxoma, myxoid liposarcoma and myxofibrosarcoma). No staining with anti-KL1 allowed us to exclude chordoma. Curative surgery was not possible. Both patients were given radiotherapy and the tumor regressed in one.     

Distribution of melanoma specific antibody (HMB-45) in benign and malignant melanocytic tumours

Summary The distribution of a recently produced melanoma specific antibody (HMB-45) has been evaluated histochemically on paraffin sections in a large panel of melanocytic and non melanocytic tumours. Results have been compared with the presence of S-100 protein. HMB-45 was shown to be a highly specific antibody being present only in melanomas, junctional melanocytes and histogenetically related neoplasms such as melanocytic neuroectodermal tumour of infancy and, at low levels, on a proportion of peripheral nerve sheath tumours. The high specificity of HMB-45 antibody, coupled with the greater sensitivity of S-100, makes the combined use of these markers practical in the differential diagnosis of skin tumours and of metastatic lesions of uncertain primary site.This work was supported by the Associazione Italiana per la Ricerca sul Cancro, Milano and Ministero Pubblica Istruzione (60%), Roma. Aldo Scarpa is supported by a Scholarship from the Associazione Italiana per la Ricerca sul Cancro, Milano     

Myxoid dermatofibroma on a great toe: a case report

Dermatofibroma is a common benign fibrohistiocytic tumor with many clinicopathological variants. Myxoid dermatofibroma is one of these variants, which is characterized by marked stromal mucin deposition. This report presents a case of myxoid dermatofibroma on a great toe that had been slowly growing for two years. Histopathologically, the relatively well-circumscribed dermal tumor was separated from the epidermis by a small grenz zone. The tumor tissue consisted of oval to spindle-shaped cells with well-defined cell borders and spindly condensed nuclei. No cytologic atypia or mitotic figures were found. Although most of the tumor cells were embedded in a prominently myxoid stroma, typical features of classic dermatofibroma including a storiform growth pattern and more densely packed collagen were observed at the periphery. Immunohistochemically, the tumor cells showed positive staining for CD68 and CD99, and negative staining for CD34 and S-100. Histopathological differential diagnoses of myxoid dermatofibroma include soft tissue neoplasms with myxoid tumor stroma, such as superficial acral fibromyxoma, cellular digital fibroma, superficial angiomyxoma, myxoid dermatofibrosarcoma protuberans and low-grade fibromyxoid sarcoma. Immunohistochemical staining can be useful in the differential diagnosis of these tumors. This case highlights the challenges encountered in the histopathological interpretation of myxoid dermatofibroma. Pathologists should keep in mind the diagnosis of myxoid dermatofibroma when dealing with myxoid neoplastic lesions arising on acral sites.     

Primary malignant 'triton' tumour of the lung

Two cases of malignant 'triton' tumour arising within lung parenchyma are described. The patients were a three-year-old child and a 53-year-old man. Both patients presented with shortness of breath and a large intrapulmonary mass on chest X-ray. Neither patient had a history of von Recklinhausen's neurofibromatosis. The lesions were treated by pneumonectomy. Grossly, both tumours presented as large, soft and gelatinous intraparenchymatous masses measuring 130 mm and 80 mm, respectively. Histologically, they were characterized by an atypical spindle cell proliferation embedded in an abundant myxoid stroma. Focal areas of rhabdomyoblastic differentiation characterized by large cells with abundant eosinophilic cytoplasm and occasional cytoplasmic cross-striations could be seen admixed with the atypical spindle cell elements. Immunohistochemical studies showed a focal positive reaction for S-100 protein in the atypical spindle cells embedded within the myxoid stroma, and a strong positive reaction for desmin and myoglobin in the rhabdomyoblastic areas. The child died three months after diagnosis with extension of the tumour into the thoracic cavity. The second patient has been lost to follow-up. Although rare, malignant 'triton' tumour should be considered in the differential diagnosis of primary spindle cell sarcomas of the lung.     

Immunohistochemical demonstration of S-100 protein in salivary gland neoplasms

A peroxidase-antiperoxidase technique for S-100 protein has been applied to 68 salivary glands. These included 17 pleomorphic adenomas, seven adenoid cystic carcinomas, 23 adenolymphomas and a number of other neoplasms. In addition, five specimens of myoepithelial sialadenitis ('benign lymphoepithelial lesion') and five normal parotid glands were included. Consistent results were obtained, myoepithelial cells and cells in myxoid and chondroid areas in pleomorphic adenomas staining intensely. In adenoid cystic carcinoma, on the other hand, there was no staining. The adenolymphomas possessed intensely S-100 protein-positive cells in the interfollicular lymphoid areas; these were probably interdigitating reticulum cells. In addition, branching structures, probably corresponding to Langerhans' cells, were observed in the epithelium of adenolymphomas.     

Perivascular pseudorosettes in childhood brain tumours: an ultrastructural and immunohistochemical study

Perivascular pseudorosettes (PP) in childhood central nervous system tumours were examined with light and electron microscopy and immunohistochemistry for glial fibrillary acidic protein, S-100 protein and albumin. One kind of PP at light microscopy comprised a central thin-walled vessel surrounded by a thick mantle of eosinophilic fibrillary material and rings of usually regular nuclei. Adjacent tumour tissue was compact. This type was correlated closely with ultrastructural evidence of ependymal differentiation. The central vessel showed continuous endothelium in all. Another type of PP comprised a central vessel of varying thickness surrounded by hyaline material, clearly defined tapering processes, and rings of often irregular nuclei. Adjacent tissue showed extensive edema and microcystic change. Ultrastructurally, this type showed no ependymal differentiation except in one myxopapillary ependymoma. Fenestrated vessels were seen in half of the tumours associated with this kind of PP. It is proposed that variation in vascular permeability, rather than in the structure of tumour cells, is the main cause for the difference in histological appearance of the two types of PP. Fenestrated vessels may also be responsible for the "myxoid" change in myxopapillary ependymomas. The amount of extracellular albumin showed no consistent correlation with the presence of fenestrations in vessels. A variable degree of positivity to GFAP and S-100 protein was seen in the tumours associated with both types of PPs with no clear difference in pattern.     

S-100 antigen labels neoplastic cells in liposarcoma and cartilaginous tumours

Summary S-100 antigen, originally believed to be unique to the nervous system, has recently been found in cell types of non-neuroectodermal origin such as chondrocytes and adipocytes. These findings suggested the possibility of detecting the antigen in tumours derived from such cells. Using the PAP method and an anti-ox brain S-100, the antigen was found in the cells of human chondrosarcomas, chondroblastomas and liposarcomas. In contrast, fibrous histiocytomas and fibrosarcomas, tested to verify the cellular specificity of the S-100 immunoreaction, did not exhibit S-100-containing cell types. The present data indicate the usefulness of the S-100 antigen as a diagnostic and investigative tool in defined neoplasms of non-neuroectodermal origin, such as chondroid tumours and liposarcoma.     

Myxoid variant of primary cutaneous malignant melanoma

We report a rare case of primary cutaneous myxoid melanoma. Histologically, the tumour was composed of spindle and stellate-shaped cells, embedded in a myxoid stroma. Positivity for S-100 protein and the presence of melanosomes were demonstrated in the tumour. Primary cutaneous myxoid melanoma is rare. This is the second report of such a case.     

Undifferentiated myxoid lipoblastoma with PLAG1 gene rearrangement in infant

ObjectivesTo analyze the clinicopathologic feature, diagnosis and differential diagnosis of undifferentiated myxoid lipoblastoma in infant.MethodsThe study included 2 cases of undifferentiated myxoid lipoblastoma in infant according to the molecular genetic diagnosis. The relevant clinicopathologic feature was investigated.ResultsWe describe 2 cases of undifferentiated myxoid lipoblastoma in infant. The both large circumscribed masses are located in deep soft tissue. Unlike most lipoblastoma, lobulated appearance was not obvious in one case and completely absent in another. The both cases presented prominent myxoid change with a plexiform vascular pattern. There were some spindle-shaped or stellate mesenchymal cells, while no any mature adipocytes. The initial suggestion of case 1 was myxoid liposarcoma, and case 2 was aggressive angiomyxoma. However, few S-100 positive lipoblasts suggested the origin of the tumor. FISH analysis using a PLAG1 break apart probe confirmed a PLAG1 rearrangment. The final diagnosis was undifferentiated myxoid lipoblastoma.ConclusionsThe undifferentiated myxoid lipoblastoma is a very rare tumor in infant. Histologically, prominent myxoid change, a plexiform vascular pattern and lacking of mature adipocytes make it indistinguishable from myxoid liposarcoma, PMMTI and aggressive angiomyxoma. The S-100 positive lipoblasts and genetic rearrangement of PLAG1 helps in confirming the diagnosis. Even if there were no mature adipocytes, myxoid lipoblastoma was still a diagnosis that can not be ignored in myxoid tumors in children.     

Protein S-100 in the histological diagnosis of tumors

Review deals with the use of the antibodies against protein S-100 in the diagnosis of tumours in man and experimental animals. Protein S-100 was first isolated from the bovine brain and then identified in glial and Schwann cells of the nervous system, epidermal Langerhans cells, myoepithelial cells of the salivary and mammary glands and in many other cells of various organs. In spite of the lack of specificity to any tissue antibodies against protein S-100 are widely used in the diagnosis of human tumours, mainly for the differentiation between neurogenic and soft tissue tumours (positive response to S-100 protein is regularly observed in benign schwannomas, neurofibromas and granular cell tumours while fibroblastic tumours are S100-negative), for the differentiation between nonpigmented melanomas (positive) and anaplastic carcinomas (negative). The knowledge of S-100 protein distribution in normal organ facilitates the establishment of the tumour origin. Antibodies against S-100 protein allowed one to establish the neurogenic origin of some rat soft tissue tumours which were considered otherwise to be of mesenchymal origin and gave additional proof of the neurogenic origin of the rat endocardial tumours.     

Imaging mass spectrometry of myxoid sarcomas identifies proteins and lipids specific to tumour type and grade,and reveals biochemical intratumour heterogeneity

Myxofibrosarcoma and myxoid liposarcomas are relatively common soft tissue tumours that are characterized by their so‐called myxoid extracellular matrix and have to some extent overlap in histology. The exact composition and potential role of their myxoid extracellular matrix are insufficiently understood. To gain more insight into the biomolecular content of these tumours, we have studied 40 well‐documented myxofibrosarcoma and myxoid liposarcoma cases using imaging mass spectrometry. This technique provides a multiplex biomolecular imaging analysis of the tissue, spanning multiple molecular domains and without a priori knowledge of the tissue's biomolecular content. We have developed experimental protocols for analysing the peptide, protein, and lipid content of myxofibrosarcoma and myxoid liposarcomas, and have detected proteins and lipids that are tumour‐type and tumour‐grade specific. In particular, lipid changes observed in myxoid liposarcomas could be related to pathways known to be affected during tumour progression. Unsupervised clustering of the biomolecular signatures was able to classify myxofibrosarcoma and myxoid liposarcomas according to tumour type and tumour grade. Closer examination of histologically similar regions in the tissues revealed intratumour heterogeneity, which was a consistent feature in each of the myxofibrosarcomas studied. In intermediate‐grade myxofibrosarcoma, it was found that single tissue sections could contain regions with biomolecular profiles similar to high‐grade and low‐grade tumours, and that these regions were associated with the tumour's nodular structure, thus supporting a concept of tumour progression through clonal selection. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.