AP2 protein expression as a diagnostic marker in soft tissue tumours

Purpose/Methods: The aP2 gene product (aP2 protein) is known to be expressed by preadipocytes and other immature fat cells in vitro. A mouse monoclonal antibody raised against an 18 amino acid segment of the aP2 protein was found to react with lipoblasts and fetal fat cells in paraffin sections of soft tissue tumours of adipose differentiation. In this immunohistochemical study, we have further examined the diagnostic utility of aP2 expression in distinguishing tumours of adipose differentiation from other benign and malignant soft tissue tumours.Result and discussion aP2 was strongly expressed by lipoblasts in lipoblastomas and all types of liposarcoma as well as brown fat cells in hibernomas. Optimal conditions for immunohistochemical identification of lipoblasts in tumours of adipose differentiation was noted when the antibody was diluted 1:30 to 1:50. Small lipoblast-like fat cells in pleomorphic lipoma and spindle cell lipoma also showed variable staining for aP2 at this dilution of the antibody. Most benign and malignant soft tissue tumours were distinguished by their absence of staining for aP2 protein, but some cases of myxoma, malignant fibrous histiocytoma, synovial sarcoma and leiomyosarcoma contained tumour cells which reacted for aP2. aP2 protein expression is likely to prove a useful means of distinguishing lipoblasts in liposarcoma but it should be used as part of a tumour panel to exclude expression in other forms of mesenchymal tumour.     

Primary liposarcoma of the stomach: a case report and a review of the literature

Primary liposarcoma of the stomach is rare and only seven cases have been described in the English literature. Here we report the eighth case, which occurred in a 68-year-old woman who presented with repeated tarry stools and hematemesis. Endoscopic examination revealed a large ulcerated submucosal mass at the gastric angle. The patient was treated by total gastrectomy. On microscopic examination, the tumor showed the features of a well differentiated sclerosing liposarcoma. Immunohistochemically, many spindle to stellate tumor cells were diffusely positive for vimentin and CD34. Positivity for S-100 protein was found in the adipocytic component, including lipoblasts, in addition to some spindle-shaped tumor cells. On ultrastructural examination, the spindle to stellate cells had features characteristic of fibroblasts. No recurrence or metastasis was seen during 13 months. Liposarcoma of the stomach has to be considered in the differential diagnosis with other submucosal lesions, such as gastric lipoma and gastrointestinal stromal tumor.      

Low grade fibromyxoid sarcoma: fine-needle aspiration cytology with histologic, cytogenetic, immunohistochemical, and ultrastructural correlation

BACKGROUND: Although the histologic features of the recently described low grade fibromyxoid sarcoma are well established, to the authors' knowledge there are no reports in the literature describing the cytologic features of this tumor by fine-needle aspiration. Recognition of this lesion is important because of its indolent but metastasizing nature. METHODS: The authors retrospectively reviewed their surgical pathology files for cases of low grade fibromyxoid sarcoma with a preoperative fine-needle aspiration biopsy (FNAB); three such cases were found. Immunohistochemical studies were performed in all three tumors, ultrastructural examination was performed in two tumors, and fresh tissue for cytogenetic analysis was obtained in one tumor. RESULTS: All FNABs showed similar features. The aspirates were relatively hypocellular with an abundant myxoid background; the neoplastic cells contained oval to spindle shaped nuclei with minimal pleomorphism. No capillaries or areas of fibrous tissue were identified. Cytogenetic study of one case revealed no chromosomal abnormalities. The histologic findings were characteristic for this lesion. By immunohistochemistry the tumor cells showed diffuse and strong reactivity for vimentin only; at the ultrastructural level the neoplastic spindle cells had characteristics of fibroblasts. CONCLUSIONS: The cytologic features of low grade fibromyxoid sarcoma are not specific enough for a definitive diagnosis based on FNAB alone; however, correlating the cytologic and clinical findings can narrow the range of diagnosis. The differential diagnosis includes other myxoid lesions, in particular superficial or intramuscular myxoma and myxofibrosarcoma. In addition, the immunohistochemical and ultrastructural findings support a fibroblastic origin for this neoplasm.     

Radiation-induced morphological changes and radiocurability in squamous cell carcinoma of the head and neck region. A preliminary report.

Tissue samples taken from 22 patients before and during radical irradiation of squamous cell carcinomas in the head and neck region were studied by light and electron microscopy. The changes in keratinization pattern at the ultrastructural level seemed to be correlated with the outcome of the radiotherapy. The irradiation induced several cellular changes, of which nuclear atypia was the most prominent. This atypia was considered to be mainly due to cell death rather than to an aggressive nature of the tumor, because the number of mitoses decreased at the same time. The tumor invasion pattern remained unchanged. The keratinization pattern remained almost unchanged at the light microscopical level, but a slight increase of intracellular filaments and desmosomes was found in the electron microscopic study. The amount of intercellular filaments increased in three patients out of four with complete remission (CR), but in no case with tumor dissemination (n = 3) during radiotherapy. In patients with local persistent tumor or a local recurrence (LP + LR) (n = 15) the filaments either increased, decreased or remained unchanged. The number of desmosomes either increased or remained unchanged in three of four CR patients, in 13 of 15 LP + LR patients and in only one of three patients with tumor dissemination. They decreased in two patients with tumor dissemination, but only in one case with CR and in 2 cases with LP + LR. It is suggested that changes in cytoskeleton and desmosomes might be important in anchorage of tumor cells locally and might have value for prediction of the tumor response to radiotherapy. Further studies on larger materials are, however, needed before more definite conclusions can be drawn.     

Leiomyosarcoma of the external soft tissues. A clinicopathologic, immunohistochemical, and electron microscopic study

This clinicopathologic study concerns 25 cases of leiomyosarcoma of the external soft tissues, including an immunohistochemical survey of 19 cases and an electron microscopic examination of six. There was a female preponderance in a ratio of 16:9. The most common site of tumors was the thigh (nine cases), followed by the knee (five cases). Three tumors were located in the dermis, 9 were confined down to the subcutis, 2 involved the deep fascia, and 11 involved the skeletal muscle. Superficially located tumors were smaller than deeply located ones. According to the predominant histologic features, the tumors were classified into well (6), moderately (14), and poorly (5) differentiated. In addition to the classical microscopic features, dedifferentiated areas resembling malignant fibrous histiocytoma were noted in three primary tumors and one recurrent tumor. In six tumors, the anatomical location and histologic features were highly suggestive of leiomyosarcoma arising in the venous wall. Many tumor cells immunoreactive for actin were seen in 13 and for desmin in 9 of the 19 cases. Four tumors contained a few tumor giant cells positive for alpha-1-antichymotrypsin. Ultrastructurally, the tumors were characterized by smooth muscle tumor cells showing a spectrum of differentiation of varying degrees. In two cases, histiocyte-like tumor cells were detected. The most reliable prognostic parameter was the depth of the initial tumors; all patients with a leiomyosarcoma confined down to the subcutis are living, most of them more than 5 years after excision, whereas seven of the nine patients with a tumor involving the muscle have died within 5 years after excision.     

Surrounding muscle edema detected by MRI is valuable for diagnosis of intramuscular myxoma

We recently experienced 4 cases of intramuscular myxoma and analyzed MRI findings, comparing them with histological ones. Results showed that all tumors were depicted with a homogeneous low signal intensity on T1-weighted images and a markedly high signal intensity on T2-weighted images, findings which are similar to those of cystic lesions like intramuscular ganglions. However, tumors were diffusely and finely enhanced on T1-weighted images with intravenous gadolinium administration. Three cases showed the characteristic fat rim and fat cap. A diffuse edematous lesion demonstrating intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images was also found in the adjacent muscle surrounding the tumor in 3 of 4 cases. In this lesion, tumor invasion, diffuse and severe muscle degeneration, blood and lymphatic congestion with exudates, and reactive adipose tissue formation were observed. The present results suggested that for the clinical diagnosis of intramuscular myxoma with MRI examination, the combination of three MRI signs such as homogeneous low signal intensity on T1-weighted mages, markedly high signal intensity on T2-weighted images, and an enhancement effect with contrast medium are important, but the fat rim or fat cap, and the surrounding muscle edema as detected by MRI are also characteristic and allow for a more firm diagnosis. We presume that the diffuse and severe muscle fiber degeneration induced by tumors may cause such specific surrounding muscle edema.     

Myxoma of bone in a nonhuman primate

A myxoma of the mandibles in an adult female Macaca mulatta is described. The left mandible was markedly enlarged by the tumor, which extended from the symphysis to the temporomandibular joint. The tumor had extended a short distance across the symphysis into the right mandible. It was composed of a glistening mucinous material. Radiographs of the tumor showed a large expansile radiolucent lesion of the left mandible without soft tissue involvement. Light microscopy demonstrated capillaries, stellate shaped cells with processes up to 15 mu long, very few other cell types, and an amorphous ground substance. Electron microscopic examination revealed similarity to the myxoma of bone of man. The oxytalan fibers discovered in this myxoma have not been found in myxomas before and suggest the tumor is odontogenic in origin. The incidence of spontaneous neoplasia in general and that of spontaneous oral tumors in particular in nonhuman primates are reviewed.     

心脏黏液瘤的外科治疗

目的 探讨心脏黏液瘤的诊断和治疗经验。方法 回顾性分析自1995年10月～2001年10月收治的83例心脏黏液瘤病例(其中左心房黏液瘤57例,右心房黏液瘤19例,左心室黏液瘤2例,右心室黏液瘤5例)。术前经彩色超声心动图确诊,均在体外循环下行黏液瘤摘除术,同期行二尖瓣成形术8例,二尖瓣机械瓣置换术3例,三尖瓣成形术62例,三尖瓣机械瓣置换术1例,房间隔缺损修补术6例,隔膜型主动脉瓣下狭窄解除术1例。结果 无围术期及手术死亡,随访72例,时间1个月到6年,心功能(NYHA分级):Ⅰ级51例,Ⅱ级11例,Ⅲ级4例,1例发生脑梗死死亡,1例死于车祸,1例死因不明,3例复发再次手术,复发率4.2％。结论 心脏黏液瘤一经确诊应尽快手术,手术效果满意,复发率低,彩色超声心动图对诊断及术后随访有重要作用,应注意术后随访。     

心脏黏液瘤的临床病理学特征——47例分析

背景与目的:心脏黏液瘤是心脏肿瘤中最常见的一种,形态结构多样,而生物学行为及组织发生尚存争议。本研究探讨心脏黏液瘤的临床特征、组织形态及免疫表型特点。方法:复习47例心脏黏液瘤临床资料及组织切片,对部分病例作特殊染色及10种抗体的免疫组化染色并观察其结果。结果:47例心脏黏液瘤中女性患者较多,占32例,年龄最小者3岁。肿瘤体积0.7cm×0.7cm×0.4cm～12cm×8cm×7cm,42例有蒂,5例无蒂;43例位于左心房,3例位于右心房,1例位左心室近心尖部。瘤细胞呈星芒状、梭形、圆形或不规则形,排列呈小团及索状,其间有大量黏液。4例可见瘤细胞围绕小血管排列,4例表面有一层增生纤维组织形成的假包膜,2例间质呈血管瘤样改变;7例间质有大片陈旧性出血、含铁血黄素及铁盐沉积、纤维化;1例有灶状腺样结构,1例有骨化及脂肪化生,1例富于细胞。12例作免疫组化,Vimentin及CD34肿瘤表面被覆细胞及实质内细胞为阳性;腺样分化区CK及EMA阳性;富于细胞的1例PCNA及Ki67阳性。随访21例,随访1～15年,未见复发。结论:心脏黏液瘤有腺样化生、陈旧性出血、纤维化、骨化及脂肪化生等多种继发性改变,富细胞者是否存在潜在恶性,尚待进一步研究。心脏黏液瘤可能起源于多潜能原始间叶细胞。     

Node-negative breast cancer treated by modified radical mastectomy without adjuvant therapies: variables associated with disease recurrence and survivorship

The present study attempts to identify poor prognosis subgroups of women with node-negative breast cancer that might benefit from systemic adjuvant therapy. The cases were collected through a cooperative effort of 57 surgeons at eight hospitals in the Detroit area and coordinated by the Michigan Cancer Foundation where data collection and analyses were completed. The primary treatment of all patients was a modified radical mastectomy. Of the 1,078 cases accessioned between October 1975 and April 1983, 537 were found to have no microscopic lymph node involvement and 462 of these cases received no adjuvant antineoplastic therapy. The period of follow-up of these cases (alive, n = 358) has been 78.75 +/- 24.6 months (mean +/- SD). Overall, the cumulative 6-year recurrence rate as calculated by life table analysis was 26%, with 16.8% dying of their disease. Tumor size was an important prognostic factor; the recurrence rate was 16.2% for those with primaries measuring less than or equal to 1 cm, with only a 6.3% mortality. Patients with tumors measuring greater than 5 cm also did well: 13.7% recurrence and 13.7% mortality rates at 6 years. The premenopausal women did slightly, but not statistically significantly, better than those who were postmenopausal. The presence or absence of quantifiable estrogen receptor protein (ER) was of little predictive value as far as rates of recurrence were concerned, but patients with an ER-positive tumor survived significantly longer. In postmenopausal women, those whose tumor lacked ER (n = 112) fared poorly: 30.4% experienced a recurrence by 6 years and 28% died of their disease. Recurrence rates and death rates were also high in a small group (n = 35) of postmenopausal women with ER+ tumors exhibiting nuclear pleomorphism (nuclear grade [NG]3) (38% and 24.3%, respectively). No poor prognosis group of premenopausal women was identified.     

Localized fibrous tumor (localized fibrous mesothelioma) of the liver

A case of localized fibrous tumor (LFT) (localized fibrous mesothelioma) of the liver in an 83-year-old woman is presented. The tumor was 15 x 9 x 8 cm and was confined to the left lateral segment of the liver. Occasional mitotic figures (MF) (2 to 3 per 50 high-power fields [HPF]) were present. Strong, diffuse vimentin positivity was demonstrated by immunohistochemistry. Immunoreactivity for cytokeratins (AE1-3), epithelial membrane antigen (EMA), desmin, and desmosomal proteins (desmoplakin I + II) was absent. Electron microscopic examination showed a mesenchymal appearance of the majority of neoplastic cells, with a few ultrastructural features suggestive of mesothelial differentiation. These findings supported a submesothelial origin of the tumor. After a partial hepatectomy with total gross and microscopic removal of the tumor, the patient was alive without recurrence at 2 years, 5 months later. A review of the English literature showed six additional cases that are probably similar. Currently, all tumors have been clinically benign, although follow-up information has been limited.     

Retroperitoneal liposarcoma with various histological figures

A case of retroperitoneal liposarcoma consisting of three large nodules with three different types of histologic findings is presented. A 69-year-old man was diagnosed as having a malignant tumor in the retroperitoneum and underwent successful tumor extirpation. The resected tumor had three different type of nodules, 18 X 15 X 7.0 cm, 8 X 15 X 4.0 cm, 15 X 10 X 2.5 cm in size, respectively. The histologic examination revealed myxoid, well-differentiated fibrosing and lipoma-like liposarcoma type, respectively. Chemotherapy was undertaken postoperatively, and there is no evidence of recurrence two years after surgery.     

An unusual massive head-neck tumor and its surgical management

An unusually massive (15cm x 15cm x 15cm)and heavy tumor, (2.85 kg) one of the largest of its kind, was present in a sixty years old male patient who attended the E.N.T. out-patient depart-ment. The patient was Australia antigen positive. The case presented a surgical challenge be-cause of its large size and skin adherence. Complete excision of the tumor and closure of the resultant facial defect, (5cm. x 5cm) with split-thickness skin graft was the treatment modality followed. There is no recurrence, and the prognosis appears to be good.     

Well-differentiated liposarcoma of the tongue.

Intraoral liposarcomas are rare, with most reported cases being of the myxoid histological type. We present a well-differentiated liposarcoma of the tongue, in a 65-year-old man. The tumour presented lipoblasts in various stages of differentiation, lipocytes in different sizes and shapes, mesenchymal and signet-ring cells. Lipoma, spindle-cell lipoma, myxoma, hibernoma, angiolipoma, fibrolipoma, pseudosarcomatous faciitis and malignant hysticytoma were considered in the diagnosis process. The patient was treated surgically and so far is free of disease.     

Eccrine sweat gland tumor of clear cell origin involving the eyelids.

A 47-year-old patient with an unusual tumor involving the right upper and lower eyelids has been followed for almost 6 years. The tumor has remained localized to the eyelids and has recurred locally following attempts at complete or partial excision. The morphological features of the tumor as seen by ordinary light microscopic methods were puzzling, and resulted in a variety of pathologic diagnoses. Light microscopic examination of plastic-embedded semithin sections, and electron microscopic examination indicate that this is a hitherto undescribed eccrine sweat gland tumor of clear cell origin. Its infiltrative growth pattern and tendency to local recurrence suggests that it may be a low-grade malignant neoplasm.     

Primary malignant fibrous histiocytoma of the lung. A clinicopathologic and ultrastructural study of five cases

Primary sarcomas of the lung are rare malignant neoplasms which have usually been classified as fibrosarcomas or as leiomyosarcomas. Only five cases of primary malignant fibrous histiocytoma (MFH) of the lung have previously been reported in the literature. The authors reviewed 10 cases of primary pulmonary sarcoma of the lung seen at their institution during the last 12 years, and five of these cases met the morphologic criteria for the diagnosis of MFH. The morphology in these cases is identical to MFH of other body locations, and shows a combination of fibroblast-like and histiocyte-like cells at both the light and electron microscopic level. By electron microscopic examination there was no evidence for anaplastic carcinoma, rhabdomyosarcoma, or leiomyosarcoma. Of the three patients with adequate follow-up, one patient is alive without evidence of disease at 10 years, one died at 5 years without evidence of recurrent sarcoma, and one died at 7 months with liver metastasis. Two other patients are alive without recurrence at 8 months and 1 year, respectively, following surgery. Because MFH is primarily a tumor of the soft tissues of the extremities, patients with MFH of the lung must be carefully evaluated to rule out a metastatic origin. The reported prognosis in patients with primary MFH of the lung is poor, but early surgical resection does offer the possibility of a cure.     

Malignant smooth muscle tumors of the retroperitoneum and mesentery: a clinicopathologic analysis of 44 cases

Forty-four cases of leiomyosarcoma arising in the retroperitoneum (33 cases) and mesentery (11 cases) were analyzed clinicopathologically, and four were examined ultrastructurally. These tumors were more common in women (61%) than in men (39%), and the median age of the patients was 59 years. Except for three tumors, most were large and over 10 cm in the greatest diameter. Twenty-seven tumors were classical leiomyosarcomas, while seven were composed predominantly of epithelioid cells and classified as malignant leiomyoblastoma (epithelioid leiomyosarcoma). In addition to the classical microscopic features, dedifferentiated areas resembling malignant fibrous histiocytoma were noted in three cases. Ultrastructurally, the tumors were characterized by smooth muscle tumor cells showing a spectrum of differentiation of varying degrees. Of the 42 patients for whom follow-up information could be obtained, 33 (79%) died within a period of five years after the initial treatment. Mitotic activity showed no significant correlation with biological behavior; ten of the 15 patients in whom the mitotic counts were less than five per 10 high-power fields (HPF), expired of the tumor.     

Clinical and Histopathological Analysis of 66 Cases withCardiac Myxoma

Background and Purpose: Cardiac myxoma is a major primary heart tumor which often causes unexpectedsymptoms or sudden death. This present study was designed to investigate its clinical pathological features andbiological behavior. Methods: A retrospective analysis of the clinical pathologic and immunohistochemical featuresof 66 cases with cardiac myxoma was conducted. Results: In 66 patients with cardiac myxoma, 61 cases hadinvolvement of the left atrium, one case in both the right ventricular and left atria. The female: male ratio was2.7:1. Patients had symptoms of blood flow obstruction and systemic alterations with performance of arterialembolization. Tumors were spherical, lobulated or irregular in shape, and soft and brittle. Immunohistochemicalmarkers of vimentin and CD34 in tumor cells were positive. Conclusion: Cardiac myxoma always exists in theleft atrium and is more common in women, with diverse clinical manifestations and pathomorphism. Althoughproliferative activity and the recurrence rate are low, in addition to thorough surgical resection, strengthenedreview is important for young patients.     

Angiomatoid malignant fibrous histiocytoma: a distinct fibrohistiocytic tumor of children and young adults simulating a vascular neoplasm.

This article describes 41 examples of an unusual fibrohistiocytic sarcoma which occurred primarily in the extremities of young individuals between the ages of 5 and 25 years (median 13 years). It manifested as a nodular subcutaneous growth that seldom caused tenderness or pain, and clinically was often mistaken for a hematoma or a hemangioma. Grossly, the tumor presented as a circumscribed, multinodular or multicystic, hemorrhagic mass that ranged in size from 0.7 to 10 cm (median 2.5 cm). On microscopic examination, it consisted principally of 1) solid arrays or nests of fibroblast- and histiocyte-like cells, not infrequently containing varying amounts of intracellular hemosiderin or lipid, 2) focal areas of hemorrhage or hemorrhagic cyst-like spaces, sometimes occupying the major portion of the tumor, and 3) aggregates of chronic inflammatory cells, chiefly lymphocytes and plasmacytes, a feature that caused confusion with a lymph node metastasis in several cases. Follow-up information, available in 24 patients, revealed a variable clinical course. Twenty-one patients were alive, 11 with recurrence (including one with 9 recurrences in a 21-year period) one with recurrence and metastasis and one with metastasis. Three patients had died of metastasis 1, 3, and 13 years respectively, after the initial surgical therapy. The exact histogenesis is still obscure. Most likely it is a tumor of fibroblast- and histiocyte-like cells, akin to malignant fibrous histiocytoma, but different in its age incidence, microscopic appearance and behavior.     

Estrogen Receptor- and Progesterone Receptor-Positive Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma: A Case Report

The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is a relatively rare tumor. We herein report the case of young woman with DSV-PTC who developed cervical lymph node recurrence 7 years after the initial surgery. A 15-year-old female patient with no medical or family history of thyroid tumors developed a thyroid neoplasm in the right lobe. Right thyroidectomy and regional lymphadenectomy were performed, and the tumor was diagnosed as DSV-PTC. She was followed up as an outpatient. Seven years after the surgery, cervical lymph node recurrence developed. On microscopic examination, the thyroid tumor showed a papillary growth pattern with numerous psammoma bodies and distinct fibrosis. Immunohistochemically, the tumor cells were estrogen receptor and progesterone receptor positive with reduced membranous expression of E-cadherin and were intermingled with S-100-positive dendritic/Langerhans cells. DSV-PTC is characterized by a strong tendency for invasion and metastasis. Thus, accurate diagnosis is clinically important, and a morphological and immunohistochemical understanding of DSV-PTC is necessary.Key words: Diffuse sclerosing variant of papillary thyroid carcinoma, Estrogen receptor, Progesterone receptor, E-cadherin, S-100, Immunohistochemistry