Yoichi Hachitanda

Pleomorphic leiomyosarcoma: clinicopathologic and immunohistochemical study with special emphasis on its distinction from ordinary leiomyosarcoma and malignant fibrous histiocytoma.

Pleomorphic leiomyosarcoma (PLMS) was recently described as a morphologic variant of leiomyosarcoma; however, its diagnostic criteria, as shown by morphologic features and biologic behavior, remain controversial. We describe 28 cases of pleomorphic sarcoma with pleomorphic areas in more than two thirds of the tumor and an ordinary leiomyosarcomatous fascicular area covering less than one third as PLMS. PLMS comprised 8.6% of all the leiomyosarcomas (322 cases) registered in our institute. Patients ranged in age from 31 to 89 years (average, 57.9 years). Seventeen patients (60.7%) were male and 11 were female. Tumor location was as follows: the extremities in 17 cases, the retroperitoneum or abdominal cavity in 7 cases, the chest/abdominal wall in 3 cases, and the scalp in 1 case. Histologically, all cases showed at least small foci of fascicles consisting of smooth muscle tumor cells, in addition to pleomorphic areas mimicking storiform–pleomorphic malignant fibrous histiocytoma. The border between pleomorphic and leiomyosarcomatous fascicular areas was sharp in 3 cases, gradual in 2 cases, and blending in 23 cases. Sixteen cases (57.1%) showed a typical storiform pattern, 6 cases revealed extensive stromal hyalinization, 6 cases showed a chronic inflammatory infiltrate, 2 cases had the foci of foamy xanthomatous cells, and 7 cases contained myxoid malignant fibrous histiocytoma-like areas covering less than 50% of the tumor. The tumors had a tendency to be of a morphologically higher grade (10 tumors were French Federation of Cancer Centers grade 2, 18 were grade 3). Five of 28 cases (18%) showed rhabdoid features. Immunohistochemically, all of the 28 tumors examined showed a positive reactivity for at least one smooth muscle marker (desmin, muscle-specific actin, and &agr;-smooth muscle actin) in the leiomyosarcomatous fascicular areas. In the pleomorphic areas the expression of smooth muscle markers (desmin 10 of 28, muscle-specific actin 13 of 28, and &agr;-smooth muscle actin 14 of 28) was significantly reduced, compared with that in leiomyosarcomatous fascicular area (desmin 18 of 28, muscle-specific actin 26 of 28, and &agr;-smooth muscle actin 24 of 28). No significant difference was observed between the MIB-1 labeling index in the leiomyosarcomatous fascicular areas (26.10 on average) and that in the pleomorphic areas (26.17 on average). However, the MIB-1 labeling index in PLMS was significantly higher than that in ordinary leiomyosarcoma (n = 20, 12.86 on average) or storiform–pleomorphic malignant fibrous histiocytoma (n = 16, 16.63 on average). In 23 patients follow-up data were available with a duration of 1–239 months. Eleven patients developed metastases, and lung accounted for the most common site of metastasis (9 cases). Fifteen of 23 patients (65.2%) died of disease. Our results indicate that PLMS should be differentiated from ordinary leiomyosarcoma because of its high proliferative activities and rather aggressive biologic behavior.

Reassessment and clinicopathological prognostic factors of malignant fibrous histiocytoma of soft parts

Recently, the category of malignant fibrous histiocytoma (MFH) has been under discussion and new entities resembling MFH have appeared. To clarify the recent situation regarding MFH, we reassessed previously diagnosed MFH cases in accordance with the most up‐to‐date diagnostic criteria, which included allied tumors. We carefully reassessed 428 cases that had been diagnosed in our institute during the past 28 years. Moreover, we searched for clinicopathological prognostic factors among the cases that were finally diagnosed as MFH. Among the 428 cases, 138 cases had their diagnoses changed. The revised cases included 78 leiomyosarcomas (57%; ordinary leiomyosarcoma, 45 cases; pleomorphic leiomyosarcoma, 23 cases; myxoid leiomyosarcoma, 10 cases), 12 liposarcomas (9%; pleomorphic liposarcoma, 11 cases; dedifferentiated liposarcoma, one case), seven dermatofibrosarcoma protuberans (5%), six unclassified sarcomas (4%), five primary or metastatic carcinomas (4%), four low‐grade fibromyxoid sarcomas (3%), four inflammatory myofibroblastic tumors (3%), three rhabdomyosarcomas (2%), three malignant peripheral nerve sheath tumors (2%), three acral myxoinflammatory fibroblastic sarcomas (2%) and two atypical fibroxanthomas (1.5%). Among the 1974 soft tissue sarcomas registered in our institute, MFH (428 cases) had been the most common sarcoma, followed by liposarcoma, leiomyosarcoma and rhabdomyosarcoma. However, after reassessment, leiomyosarcoma proved to be the most common soft tissue sarcoma (322 cases), followed by 290 MFH, 273 liposarcomas and 202 rhabdomyosarcomas. Among these 290 cases finally diagnosed as MFH, survival data were available in 189 cases. Tumor location in the abdominal cavity, the retroperitoneum or the head and neck (P = 0.0024), tumor size of 5 cm or more (P < 0.0001), deep tumor location (P < 0.0001), high histological grade (grade 3) based on the French Federation of Cancer Centers’ grading system (P = 0.0007), and high stage (stage III or IV) based on the American Joint Committee on Cancer (AJCC) staging system (P < 0.0001) were significantly worse prognostic factors by univariate analysis. In multivariate analysis, deep tumor location and high AJCC stage were independent adverse prognostic factors. We conclude that leiomyosarcoma is the most important differential diagnosis for MFH, especially pleomorphic leiomyosarcoma from storiform–pleomorphic type and myxoid leiomyosarcoma from myxoid type. Tumor depth and AJCC stage are the most important predictive prognostic factors in MFH.

Undifferentiated (embryonal) sarcoma of the liver. A tumor of uncertain histogenesis showing divergent differentiation.

Pathologic features of eight cases of undifferentiated (embryonal) sarcoma of the liver (USL) in childhood were studied. Light microscopic examination showed a diffuse growth of spindle cells with occasional polygonal cells and multinucleated giant cells and also revealed focal areas of storiform pattern in four tumors, cambium layer formation in one tumor, and alveolar arrangement in one tumor. Immunohistochemical study showed positive staining of proliferating cells for suggestive histiocytic markers (A1AT in 6/6, A1ACT in 5/6, lysozyme in 4/6, and KP1 in 4/6) and for muscle markers (desmin in 4/6 and HHF35 in 3/6). Ultrastructural examination demonstrated that the individual tumors were composed of a mixture of cells having fibroblastic, histiocytoid, fibrohistiocytoid, myofibroblastic, and undifferentiated (primitive mesenchymal) morphologies. Also identified were cells with definite myoblastic morphology in three tumors: leio-myoblastic in one and rhabdomyoblastic in two. In conclusion, the tumor cells in USL show phenotypical diversity comparable to those of malignant fibrous histiocytoma with or without additional rhabdomyosarcomatous or leiomyosarcomatous differentiation.

Extraskeletal myxoid chondrosarcoma in young children

Two extraskeletal myxoid chondrosarcomas with a solid soft tissue mass occurred on the right upper arm of a 4‐year‐old boy and on the chest wall of a 1‐year‐old boy. Microscopically, both tumors were characterized by lobular configuration and were sparsely cellular with a background of myxoid matrix. The cells were small and round, and appeared undifferentiated, sometimes with a narrow eosinophilic cytoplasm. They grew in nests or strands and sometimes in a single file. They were strongly positive for S‐100 protein and vimentin. Ultrastructural features suggested that the cells had a poorly differentiated mesenchymal nature with chondrocytic differentiation. These are the sixth and seventh reported cases of extraskeletal myxoid chondrosarcoma occurring in children. There are definite differences between this tumor with immature features and the extraskeletal myxoid chondrosarcoma in adults. Problems of differential diagnoses from other small round cell sarcomas also are discussed.

Pleuropulmonary blastoma in childhood: a tumor of divergent differentiation

Pleuropulmonary blastoma (PPB) is a rare and highly aggressive tumor in children and is distinct from ordinary pulmonary blastoma or carcinosarcoma of the lung. This report describes the phenotypical characteristics of seven PPB tumors. The patients were five females and two males, all diagnosed in their third year of life. Five tumors were located within the pulmonary parenchyma, one in the mediastinum, and one involved both lung and mediastinum. Two children are alive and five have died of disease. Histologically, PPB showed a diffuse proliferation of undifferentiated blastemal cells with additional areas of chondroblastic foci (six tumors), storiform pattern (three tumors), alveolar pattern (one tumor), and lipoblastic differentiation (one tumor). Immunohistochemically, tumor cells were positive for vimentin in five of five tumors, histiocytic markers (A1AT and A1ACT, four of six cases; lysozyme, two of six; KP1, three of five) and myogenic markers (desmin, four of six; HHF35, five of six). S-100 was expressed in the chondroblastic areas (in three of four cases). Epithelial membrane antigen and cytokeratin were positive only in epithelial or mesothelial cells entrapped in the tumor. Ultrastructural examination demonstrated a similarity between the proliferating cells in PPB and those seen in malignant fibrous histiocytoma; that is, PPB tumor was mainly composed of a mixture of primitive, fibroblastic, myofibroblastic, histiocytoid, and fibrohistiocytoid cells. Also identified were cells with rhabdomyoblastic differentiation (two tumors) showing thick and thin filaments with Z-discs. In conclusion, PPB showed phenotypical diversity and was composed of MFH-type cells and cells with more specific mesenchymal differentiation

Expression of intercellular adhesion molecules in epithelioid sarcoma and malignant rhabdoid tumor

We clinicopathologically evaluated 31 cases of epithelioid sarcoma (ES; 25 ‘classical’ type and six ‘proximal variant’ type) and six cases of malignant rhabdoid tumor (MRT; three extrarenal and three renal). We also did immunohistochemical studies on 12 classical and three proximal variant cases of ES, and six cases of MRT, to clarify the differences in biological behavior in these tumors. E‐cadherin, β‐catenin and CD34 expression was evaluated. We also carried out mutational analysis of exon 3 of the β‐catenin gene by polymerase chain reaction–single‐strand conformation polymorphism analysis. In ES, the 5‐ and 10‐year survival rates were 71.1 and 55.3%, respectively. A high mitotic rate (>15/10 high‐power fields) was significantly correlated with a poor overall survival rate in ES (P = 0.0248). E‐cadherin expression was observed in nine cases (69.2%) of ES and in four cases (66.7%) of MRT. Most of these tumors showed aberrant E‐cadherin expression. Seven cases (46.7%) of ES were positive for CD34, although none of the cases of MRT were CD34 positive. Eleven cases (73.3%) of ES were positive for β‐catenin, which was localized to the cellular membrane, whereas all of the cases of MRT were β‐catenin negative. Mutational analysis for the β‐catenin gene was done in nine cases of ES and six cases of MRT, however, genetic alteration was not found. From our results, we conclude that β‐catenin membranous expression could be a useful marker for distinguishing ES, including the proximal variant, from MRT.

Melanotic neuroectodermal tumor of infancy : a case report of paratesticular primary with lymph node involvement

: A 17-month-old boy had a melanotic neuroectodermal tumor of infancy in the left paratesticular region affecting the retroperitoneal lymph nodes. Immunohistochemical and ultrastructural study showed phenotypical diversity of the proliferating cells within a spectrum of neuroectodermal differentiation. Urinary catecholamine levels were initially elevated but returned to normal values after complete eradication of the tumor. The patient received chemotherapy and is now well, without evidence of disease 28 months after surgery.

Prognostic VaIue of N-myc Oncogene Amplification and S-100 Protein Positivity in Children with Neuroblastic Tumors

Data on 43 neuroblastic tumors (30 neuroblastomas and 13 ganglioneuroblastomas) obtained from 22 untreated and 21 pretreated children, were analyzed to determine the correlation between N‐myc oncogene amplification and immunohistochemically identified S‐100 protein positivity. Sixteen patients In whom the tumor showed significant amplification of N‐myc (more than ten copies) died, irrespective of S‐100 protein positivity and other conventional factors. Among 27 patients with low amplification of N‐myc (less than ten copies), the estimated progression‐free survival for those whose tumors had numerous S‐100 protein‐positive cells (P group), and few or no positive cells (N group) was 75% and 17%, respectively (p<0.0001). Thus, in addition to N‐myc oncogene amplification as a reliable indicator of outcome, S‐100 protein positivity should be useful for prediction of prognosis in children with neuroblastic tumors showing low amplification of N‐myc. Correlations among these results and other clinical factors are briefly discussed. Acta Pathol Jpn 42: 639–644, 1992.

Mixed tumor of deep soft tissue

Mixed tumors of the salivary gland and skin are relatively common but are quite rare in soft tissue. It is believed that, as in the salivary gland form, most of these lesions are benign, but that a small subset behave in an aggressive fashion. We report here a patient with recurrent mixed tumor of soft tissue with infiltrative growth. The primary tumor arose in deep subfascial soft tissue of the right lower leg and was adjacent to the surface of the fibula. An open biopsy and complete resection were performed. Upon histological examination of the resected specimen, neoplastic cell infiltration at the tumor/soft tissue interface was not obvious; local recurrence, however, was observed 1 year later. The patient was treated with wide resection. Histological examination confirmed that the recurrent tumor with an extensive chondroid area invaded the osseous tissue of the fibula. At present, 1 year after the second resection surgery, there is no evidence of disease.

Cytogenetic and clinicopathological analysis of soft-tissue leiomyosarcomas.

To identify a characteristic cytogenetic aberration and cytogenetic‐morphological correlation in soft‐tissue leiomyosarcomas, a karyotypic and clinicopathological analysis of 15 cases of leiomyosarcoma was performed. The histological type was classical in nine cases, pleomorphic in three cases and myxoid in three cases. The histological grade was 1 in three cases, 2 in 10 cases and 3 in two cases. Nine of 15 tumors displayed an abnormal karyotype, whereas the other six tumors displayed a normal karyotype. The relative consistency of involvement of 3p, 3q, 6q, 7p, 7q, 9p, 10p, 11p, 11q, 12p, 16q, 17p and 19q was recognized, although characteristic chromosomal rearrangements were not detected. All six tumors that had a normal karyotype were of the classical type, whereas those displaying an abnormal karyotype contained another morphological type along with the classical type. The results of the present study suggest that chromosomal aberrations contribute to morphological changes in soft‐tissue leiomyosarcomas.