Long survival of a woman with a huge leiomyosarcoma of the duodenum after pancreaticoduodenectomy and transverse colectomy: a case report.

A woman with a huge leiomyosarcoma of the duodenum that had invaded the pancreas and transverse colon is living and well 10 years after pancreaticoduodenectomy combined with resection of the transverse colon. Malignant potential of the tumor was determined by the mitotic rate and nuclear deoxyribonucleic acid content. The mass exceeded 10 cm yet was characterized by low mitotic activity and a near-diploid pattern. The long survival is attributed to the extensive surgery and low-grade malignancy of the tumor.

The diagnostic utility of desmin. A study of 584 cases and review of the literature.

The diagnostic utility of several antibodies against desmin and their optimal staining conditions have not been systematically evaluated. Sections of paraffin-embedded tissues from 584 cases were stained with a monoclonal antibody against desmin (Clone DER 11 from DAKO), using an avidin-biotin-peroxidase technique. The results were tabulated and compared with those from previous reports. The following observations were made: (1) When pronase digestion was performed before staining, desmin was equally demonstrable in tissues fixed in formalin, Zenker's, Bouin's, or B5 fixative; however, desmin staining was lost or significantly diminished in tissues fixed in absolute ethyl alcohol. In contrast, when pronase was not used, a positive staining was demonstrated only in tissue fixed in absolute ethyl alcohol. (2) Positive staining was found in normal muscle (92 of 92 cases), leiomyoma (12 of 13), rhabdomyoma (6 of 6), rhabdomyosarcoma (31 of 31), leiomyosarcoma (18 of 26). (3) Desmin was never found in epithelia, normal mesenchymal tissue other than muscle, tumors stimulating rhabdomyosarcoma, and epithelial tumors. (4) A positive staining was documented in 1 tumor (a fibrous histiocytoma) of 42 benign predominantly spindle cell tumors and in 8 of 89 predominantly spindle cell sarcomas. (5) Desmin was never documented in myoepithelial cells but stained myofibroblasts in 2 of 12 examples of granulation tissue and in 29 of 67 samples containing tumor-associated desmoplasia. The authors' data on the diagnostic sensitivity and specificity of the evaluated antibody should improve the use of desmin in diagnostic pathology.

[Vesical leiomyosarcoma. Immunohistochemical and ultrastructural study]. / Leiomiosarcoma vesical. Estudio inmunohistoquímico y ultraestructural.

A case of poorly-differentiated leiomyosarcoma of the bladder is described. Diagnosis was established by immunohistochemical and ultrastructural analyses. The therapeutic possibilities in this aggressive tumor type are described.

Epithelioid leiomyosarcoma of the left atrium: immunohistochemical and ultrastructural findings.

Leiomyosarcomas of the heart are rare, with only 12 cases reported in the literature. An example of the epithelioid variant of leiomyosarcoma is described. The tumour cells expressed vimentin, desmin, muscle-specific actin and smooth muscle-specific actin. In addition, they were also labelled by monoclonal and polyclonal antibodies to cytokeratin intermediate filaments and displayed cell junctions at the ultrastructural level, features which highlight the potential pitfalls in the application of immunohistochemistry and electron microscopy in the diagnosis of poorly differentiated tumours.

Primary recurrent leiomyosarcoma of the breast. Case report with ultrastructural and immunohistochemical study and review of the literature.

The authors report a case of recurrent mammary leiomyosarcoma in a 50-year-old woman. The neoplasia, with a recognized clinical evolution of 11 years, was resected on two occasions and had not metastasized. Microscopic examination showed 4 mitoses/10 high-power fields, moderate cytologic atypia, and, ultrastructurally, abundant myofibrils with condensations. Immunoperoxidase stains had positive results for muscle-specific antigen and showed focal reactivity for epithelial membrane antigen and S-100 protein. Analysis of the ten cases (including the present one) reveals that this neoplasm has appeared with greater frequency in women with an average age of 52 years. All neoplasms have been limited to the breast at the time of diagnosis. As a group, they have better prognosis than other sarcomas of the breast, although the possibilities of recurrence or dissemination exist, even many years after the primary extirpation. The size of the tumor and mitotic activity seem to be of little prognostic value. Mammary leiomyosarcoma shares clinical and pathologic similarities with subcutaneous leiomyosarcoma in other anatomic sites.

Malignant peripheral nerve sheath tumors and spindle cell sarcomas: an immunohistochemical analysis of multiple markers.

An immunocytochemical study using a panel of commercially available antisera, has been performed to distinguish on the basis of their immunoreactivity a series of spindle cell sarcomas diagnosed solely on the histologic features: 11 malignant schwannomas (MS), 8 leiomyosarcomas (LMS) and 3 malignant fibrous histiocytomas (MFH). The results have been compared with those obtained in 12 benign and 8 malignant peripheral nerve sheath tumors (MPNST) in which the microscopic diagnosis was supported by their origin in a nerve trunk and/or in von Recklinghausen's (vR) disease. The following antisera were used: anti-S-100 protein, anti-Leu-7, anti-neuron specific enolase (NSE), anti-myelin basic protein (MBP), anti-glial fibrillary acidic protein (GFAP) and anti-actin. S-100 protein was present in 100% of benign and malignant peripheral nerve tumors and in 7/11 (63%) of MS diagnosed on histological basis only and in 3/8 (37%) LMS. MFH were negative. Leu-7 positivity was observed in 8/12 (66%) and 6/8 (75%), respectively, in benign and malignant PNS neoplasms, in 5/11 (45%) MS, 4/8 (50%) LMS and 2/3 (66%) MFH. NSE was present in 7/12 (58%) and 6/8 (75%), respectively, in benign and malignant PNS tumors, in 6/11 (54%) MS and in 1/8 (12%) LMS. MFH were negative. MBP resulted negative in peripheral nerve neoplasms and spindle cell sarcomas. GFAP positivity was observed in 2/12 (16%) and 1/8 (12%), respectively, in benign and malignant PNS neoplasms. All spindle cell sarcomas were negative. All cases of MPNST and spindle cell sarcomas showed actin immunoreactivity. These results indicate that: (1) MBP, Leu-7 and NSE do not represent markers of schwannian differentiation; (2) GFAP, although rarely expressed, may indicate schwannian differentiation, and (3) malignant peripheral nerve neoplasms and LMS share immunoreactivity for S-100, Leu-7, NSE and actin, therefore they cannot be differentiated on immunocytochemical basis using commercially available antisera.

Immunohistochemical evaluation of intermediate filament expression in canine and feline neoplasms.

Specimens of neoplastic tissues from 19 dogs and 4 cats were examined immunohistochemically for intermediate filament expression, using commercially available antibodies. Staining was observed in a wide range of tumor tissues and in normal internal controls by use of antibodies to vimentin, desmin, glial fibrillary acidic protein, and low and high molecular weight cytokeratins. Intermediate filament expression was found to be consistent with light and/or electron microscopic findings, and hence believed to be an accurate indicator of tumor histogenesis in cats and dogs. Three fixatives were evaluated for their relative abilities to preserve antigenicity. Absolute alcohol was superior to B5 fixative and both were superior to formalin. Some tissues that clearly displayed intermediate filament antigens with alcohol and B5 fixative failed to stain when fixed in formalin.

[Determination of cell nuclear DNA content in leiomyoma and leiomyosarcoma of gastro-intestinal tract (G-I)].

Nuclear DNA content was measured by microspectrophotometry in 15 biopsy specimens from patients with G-I smooth muscle tumors (3 leiomyomas and 12 leiomyosarcomas subdivided into 3 groups with 4 cases to each). The mean DNA value increased steadily as follows: leiomyomas (14.39 +/- 0.62 Au); leiomyosarcoma Grade I (19.78 +/- 2.39 Au); Leiomyosarcoma Grade II (26.39 +/- 1.60 Au); leiomyosarcoma Grade III (30.66 +/- 2.39 Au). The difference of DNA value in the 4 groups had statistical significance (P less than 0.05-0.01). These results suggest that microspectrophotometric measurement of nuclear DNA content may serve as an objective quantitative method for diagnosis of G-I tract smooth muscle tumors and classification of leiomyosarcoma.

[Experimental study of the treatment of uterine leiomyosarcoma in the mouse with progestogen].

Because of its rare occurrence in the human, the endocrinologic and receptor-related aspects of an uterine leiomyosarcoma (LMS) are poorly understood when compared to what is known of, say, human endometrial cancer. Thus, to increase our understanding, we have succeeded, by the string method, in inducing an uterine LMS in the mouse and have studied the possibility of hormonal therapy as a method of treatment. The findings of our study are enumerated as follows: 1. The induced uterine LMS had an estrogen receptor, which was confirmed by a biochemical assay and, morphologically, by a PAP (the peroxidase anti-peroxidase technique); 2. The growth of this tumor was significantly inhibited by MPA (medroxyprogesterone acetate) therapy (100 mg/kg); 3. After MPA therapy, the estrogen receptor levels were increased, especially in the nucleus; and, 4. The growth of a secondary tumor, transplanted after the initial hormone therapy, was not inhibited by the readministration of MPA. Our results suggest that this experimentally-induced uterine LMS in the mouse provides a useful means to study therapeutic treatment, and may assist in furthering our understanding of human uterine LMS and lead to finding an effective therapy.

Primary cutaneous leiomyosarcoma. A histological and immunohistochemical study of 9 cases, with ultrastructural correlation.

Leiomyosarcoma (LMS) of dermal and subcutaneous tissues is an uncommon neoplasm. In order to analyze the specialized pathologic features of this tumor, we undertook a histological, ultrastructural, and immunohistochemical study of 9 superficial LMS, including 7 dermal lesions and 2 subcutaneous neoplasms. These were compared with 12 examples of "deep" extracutaneous LMS. Metastases to the skin from two of the latter neoplasms were also examined. Immunohistochemistry was found to be a useful diagnostic adjunct to light microscopic and ultrastructural studies in that all LMS coexpressed vimentin and desmin, regardless of site, and 90% also expressed muscle-specific actin. Variable expression of cathepsin B and myelin basic protein was noted in 8 and 10 tumors, respectively, whereas none contained cytokeratin. Weak cytoplasmic positivity for epithelial membrane antigen was seen in 1 dermal and 3 extracutaneous LMS. Of 7 dermal LMS, 4 contained S-100 protein, whereas this determinant was found in only 1 of 12 extracutaneous tumors. Conversely, Leu 7 reactivity was present in 7 of 12 extracutaneous LMS, but only 2 of 9 superficial lesions. Review of clinical features confirmed that subcutaneous LMS is capable of aggressive behaviour, whereas dermal LMS was more likely to behave in an indolent fashion. However, one example of dermal LMS exhibited aggressive local recurrences and distant metastasis, ultimately leading to the death of the patient. Therefore, careful clinical followup is indicated in all cases.

Spindle-cell and pleomorphic neoplasms of the skin. A clinicopathologic and immunohistochemical study of 30 cases, with emphasis on "atypical fibroxanthomas".

Atypical fibroxanthoma belongs to the family of spindle-cell and pleomorphic neoplasms of the skin. The lineage of differentiation of this tumor and the means whereby it can be diagnostically separated from other similar morphologic entities have been controversial. In order to address these issues, the authors studied 30 spindle-cell and/or pleomorphic cutaneous tumors, including atypical fibroxanthomas (AFXs), superficial malignant fibrous histiocytomas (MFHs), dermatofibrosarcoma protuberans (DFSPs), sarcomatoid squamous-cell carcinomas (SCCs), spindle-cell malignant melanomas (MMs), and leiomyosarcomas, (LMSs). These cases were analyzed using a panel of eight antibodies and the immunoperoxidase technique. AFXs were reactive for vimentin, alpha-1-antichymotrypsin (AACT), alpha-1-antitrypsin (AAT), and cathepsin-B (CB) but failed to display cytokeratin (CK), epithelial membrane antigen (EMA), S-100 protein, and desmin. MFHs and DFSPs exhibited immunophenotypic profiles that were nearly identical to that just described. In contrast, SCCs were typified by positivity for CK and EMA; MMs exhibited uniform reactivity for S-100 protein; and LMSs contained desmin in four of five cases. A surprising result was the expression of S-100 by LMSs. Also, all tumors displayed at least one of the three proteolytic enzymes assessed in this study (AAT, AACT, and CB), demonstrating the relative diagnostic nonspecificity of these determinants. It is concluded that AFXs are "fibrohistiocytic" neoplasms, with substantial morphologic and immunohistochemical similarity to MFHs. The immunohistochemical classification of spindle-cell and pleomorphic tumors of the skin necessitates the use of antibody panels to assess the presence of markers that are characteristic of each diagnostic group.

Immunohistochemical evaluation of Leu-7, myelin basic-protein, S100-protein, glial-fibrillary acidic-protein, and LN3 immunoreactivity in nerve sheath tumors and sarcomas.

The collective expression of five antigens produced in immature or mature myelin-producing glia was evaluated in nerve sheath tumors and spindle cell sarcomas with histologic features of schwannomas. Myelin-associated glycoprotein (Leu-7), myelin basic-protein (MBP), S100-protein, and, in most cases, glial-fibrillary acidic-protein (GFAP) and HLA-DR/Ia (LN3) immunoreactivity were evaluated immunohistochemically using commercially available antibodies on 53 benign nerve sheath tumors and 12 sarcomas. Leu-7 immunoreactivity was detected by a monoclonal antibody in 12 of 16 schwannomas, 12 of 20 neurofibromas, and 17 of 17 traumatic neuromas. No Leu-7 positivity was seen in the sarcomas. Distinct heavy MBP immunoreactivity, assessed using polyclonal antibodies, was identified only in all 17 traumatic neuromas. Extensive S100-protein positivity was seen in 15 of 16 schwannomas, 17 of 20 neurofibromas, and 17 of 17 traumatic neuromas. Extensive LN3 immunoreactivity was seen in Schwann cells of 50% of the nerve sheath tumors analyzed; however, it was also present in associated interdigitating reticulum cells; GFAP immunoreactivity was not detected. These data suggest that Leu-7 is an important marker of Schwann cell neoplasms, although it is not superior to S100 protein. Moreover, combined immunohistochemical evaluation of potential Schwann cell markers including Leu-7, MBP, GFAP, and LN3 using commercially available antibodies offers no advantage over analysis of S100-protein immunoreactivity alone.

Gastric submucosal tumours of neurogenic origin with neuroaxonal and Schwann cell elements.

Twelve cases of gastric submucosal tumours, originally diagnosed as leiomyoma and leiomyosarcoma, were investigated by staining with the neurogenic markers S-100 and neuron specific enolase (NSE). Three cases were, in addition, studied by electron microscopy. The tumours stained negatively for desmin, indicating that they were not of smooth muscle origin. All stained positively for S-100 and NSE. The ultrastructural features in the cases examined by electron microscopy were reminiscent of autonomic nerve structures normally present in the gastric wall. These included fine cytoplasmic processes of Schwann cells, wrapped with complete or incomplete basement membranes, and structures analogous to post-ganglionic neuroaxonal components. These tumours appear to represent a distinct type of gastric neoplasm originating from autonomic nerve elements in the stomach wall. They are different from previously described schwannomas or neurofibromas. In some of the tumours, identifiably neural elements are relatively a minor component, and the majority of the tumour cells are of undetermined origin. It is suggested that these cells may be poorly differentiated, lacking their antigenic determinants specific to neural differentiation.

Morphometry and cytophotometric assessment of DNA in smooth-muscle tumors (leiomyomas and leiomyosarcomas) of the gastrointestinal tract.

The difficulties in predicting the biologic behavior of gastrointestinal (GI) smooth-muscle tumors (leiomyomas and leiomyosarcomas) based on the usual criteria of malignancy are discussed. In order to evaluate the prognostic importance of the nuclear DNA content and nuclear dimensions, measurements were performed on Feulgen-stained sections of GI smooth-muscle tumors from 66 patients. The best discrimination between benign and malignant tumors was obtained by using DNA index and tumor size as descriptors in a linear discriminate analysis. This method separated 79% of the benign and 97% of the malignant smooth-muscle tumors. However, as with conventional criteria for malignancy, there remained a group of tumors close to the discriminating line with an indeterminate malignant potential. In an attempt to reduce the number of such indeterminate tumors, future studies will include the use of several descriptors in a multivariate analysis system and the application of flow cytometric studies to all tumors.

HHF35, a muscle actin-specific monoclonal antibody. II. Reactivity in normal, reactive, and neoplastic human tissues.

Monoclonal antibody HHF35 has previously been characterized biochemically as recognizing isotypes of actin (alpha and gamma) which are specific to muscle cells. In this study, the authors have investigated the normal and pathologic tissue distribution of HHF35-positive cells using the avidin-biotin immunoperoxidase method on methacarn-fixed, paraffin-embedded sections of human tissue. In addition to muscle tissues (smooth, skeletal, and cardiac) the antibody localizes to myoepithelium, as well as most of the capsular cells of several parenchymal organs, including liver, kidney, and spleen, with extension of the latter cells into the splenic trabeculaes. In pathologic tissues, the antibody localizes to cells, identified by some investigators as "myofibroblasts," in the stroma of certain tumors, within hyperplastic fibrous tissue responses ("fibromatoses") such as Dupuytren's contracture, and within fibrotic lung tissue. HHF35 also localizes to cells that proliferate within the intima in lesions of atherosclerosis and to a unique population of reactive mesothelial and submesothelial cells. Among tumors, it is positive only on leiomyomas, leiomyosarcomas, and rhabdomyosarcomas, and negative on all nonmuscle sarcomas. This antibody thus shows great potential utility as a diagnostic reagent in various pathologic conditions, most especially in the diagnosis of tumors of muscle origin.

Immunohistochemical demonstration of desmin in canine smooth muscle tumors.

Sections of formalin-fixed, paraffin-embedded canine leiomyomas, leiomyosarcomas, or fibrosarcomas were examined by immunohistochemical methods for the presence of desmin. Twenty-two leiomyomas and leiomyosarcomas were stained using the avidin-biotin complex technique, and 14 samples demonstrated positive staining for desmin. The eight negative results obtained may reflect differences in fixation or the affinity of the primary antibody for the tissues examined. Desmin was specific for myogenic tissues. Five canine fibrosarcomas examined immunohistochemically were all negative for desmin staining. The results indicate that desmin is a useful marker for immunohistochemical identification of canine leiomyomas and leiomyosarcomas.

Isolation and characterization of proteoglycans from human nonepithelial tumors.

Proteoglycans (PGs) and glycosaminoglycans (GAGs) were identified in myogenic and fibrogenic tumors. More PGs containing mainly chondroitin sulfate could be detected in malignant tumors (leiomyosarcomas) than in benign tumors (leiomyomas and fibromas). Two groups of PGs were detected in the malignant tumors by ion-exchange chromatography and gel chromatography. One group was a large molecule with chondroitin sulfate side chains, seemingly composed of two or more subpopulations that were eluted from Sepharose CL-4B with a kav of 0.45. After removal of GAG side chains from the PG by chondroitinase AC digestion, core molecules with molecular weights greater than 200,000 were obtained. Another PG detected was a fraction of small PG eluted from Sepharose CL-4B with a kav of 0.45. It consisted of a core molecule with a molecular weight approximately equal to 48,000 and GAG side chains containing chondroitin sulfate-dermatan sulfate hybrids. The mixed sequence of L-iduronic acid with D-glucuronic acid in the same GAG chain was demonstrated by the formation of a small proportion of tetrasaccharide after chondroitinase AC digestion. In the benign tumors, the large PG was found only in very small amounts, and PG detected was composed mainly of the small one eluted from Sepharose CL-4B with a kav of 0.45. Its core protein had a molecular weight of approximately equal to 46,000, which was similar to that of small PG obtained from leiomyosarcomas, but its GAG side chains were composed mainly of dermatan sulfate containing small amounts of glucuronic acid. The results suggest that the core molecules of small PGs from both benign and malignant tumors are the products of the same gene but that they are processed in a different manner to form proteoglycans with different types of GAG chains.

Neopterin as a prognostic indicator in patients with carcinoma of the uterine cervix.

In vitro, neopterin, a pyrazinopyrimidine compound, is excreted by human monocytes-macrophages after induction by supernatants from activated T-lymphocytes or by recombinant gamma-interferon. In vivo, it represents a noninvasive test for activation of cellular immune reactions. To evaluate the prognostic value of pretherapeutic urinary neopterin levels and of serial neopterin measurements during follow-up in women with cervical cancer, 1088 urine specimens from 186 consecutive patients were analyzed. Clinical assessments were made without knowledge of the results of neopterin assays (a "blinded" assessment). During the observation period (June 1980 to March 1984), 27 relapses, 18 metastases, and 26 deaths were seen. The prognostic significance of pretherapeutic neopterin and other possible prognostic clinical and laboratory parameters was tested by the univariate and multivariate Cox proportional hazards model using a stratification according to stage and surgical treatment. The combination of age at diagnosis, pretherapeutical hemoglobin, leukocyte count, and neopterin was found to predict survival best. On the basis of this result, risk groups were identified exhibiting markedly different survival behavior. A highly significant association was found between serial neopterin measurements and the risk for a relapse, metastasis, or death. The data suggest that urinary neopterin levels might be a useful adjuvant parameter in monitoring women with cervical cancer.