Pulmonary metastasis from liposarcoma: a clinicopathologic and immunohistochemical study of 24 cases.

A review of the histologic features of pulmonary metastasis and clinical implications of liposarcoma (LS) is given for 24 cases (8 each) of the 3 types of LS: myxoid LS (ML), pleomorphic LS (PL), and dedifferentiated LS (DDL). Most patients were men. Metastatic ML and PL were distributed almost equally among the lung lobes, whereas DDL was more common in the left lower lobe. The metastatic MLs had variable cellularity ranging from singly scattered cells in a hyalinized stroma (treatment-related effect) to hypercellular ML. Most PLs (6/8) were nonlipogenic and resembled an undifferentiated pleomorphic sarcoma. All metastatic DDLs had high-grade histologic features and were predictably nonlipogenic. After pulmonary metastasectomy, 2 patients with ML and 1 with PL were disease-free. The other 6 patients with ML, 7 with PL, and all with DDL had progressive disease. The morphologic features of LS metastatic to the lungs seem diverse but within the spectrum of the histologic type expected from the primary tumor. Overall, the general trend for these LS subsets is progressive disease, metastatic disease for ML and PL with a much shorter interval for PL, and metastatic disease and local recurrence for DDL.

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title: Metastatic patterns in soft-tissue sarcomas.
abstract: In 242 patients with recurrent soft-tissue sarcomas, the most common sites of initial recurrence were the primary site in 47.5% of patients and the lungs in 38% of patients. Further recurrences in the course of the disease concerned the lungs, bones, liver, and brain. Total survival and survival after recurrence were influenced by the histologic type, which also affected the site of recurrence. In the management of local recurrence, a five-year disease-free survival rate of 38% was achieved with surgical treatment, while radiation or chemotherapy alone was ineffective. Local recurrences resulted in significantly higher survival rates than those involving other organs. The disease-free interval was a significant prognostic indicator of subsequent survival in the whole group of patients and among those with local recurrence.

title: Frequent incidence of extrapulmonary sites of initial metastasis in patients with liposarcoma
abstract: The vast majority of soft tissue sarcomas spread initially to the lungs and then to other sites. The lung has been the most carefully monitored organ system during routine surveillance for a metastasis. Liposarcoma is one of the most common soft tissue sarcomas and has been noted to have extrapulmonary sites of initial metastasis. This study was undertaken to investigate both the frequency and distinguishing features of initial extrapulmonary metastasis in patients with liposarcoma.

title: Liposarcoma A study of 55 cases with a reassessment of its classification
abstract: Fifty-five cases of liposarcoma were reviewed. The cases were classified on the basis of histopathologic findings as follows: myxoid, 29 cases; well-differentiated, 11 cases; dedifferentiated, eight cases; pleomorphic, four cases; combined well-differentiated and pleomorphic, two cases; and unclassified, one case. The term “dedifferentiated liposarcoma” is proposed for tumors containing distinct areas of well-differentiated liposarcoma and cellular nonlipogenic spindle-cell or plemorphic sarcoma. All patients except one were adults. Myxoid and plemorphic liposarcoma predominantly involved the thigh, while well-differentiated, dedifferentiated, and combined well-differentiated-plemorphic liposarcoma showed a marked preference for the retroperitoneum. The survival of patients with pleomorphic and dedifferentiated liposarcoma was significantly poorer than that of those with the myxoid and well-differentiated varieties. There was a marked tendency toward local recurrence in all types. Recurrent myxoid and pleomorphic liposarcomas were often controlled by additional therapy, whereas recurrences of other types usually were not; this difference was considered largely a result of locational factors. Metastasis was observed in 10 cases of myxoid liposarcoma, three of plemorphic liposarcoma, and two of dedifferentiated liposarcoma. In myxoid liposarcoma, initial treatment consisting of excision followed by radiation resulted in a significantly reduced rate of local recurrence as compared with excision alone, and more extensive as compared with excision alone, and more extensive hypercellular zones were associated with increased metastatic potential. “Round cell” liposarcoma was not found to be an independent type; all cases for which this designation might have been considered could be better classified as myxoid liposarcoma with cellular areas (usually) or plemorphic liposarcoma with rounded cells (rarely). The resemblance of portions of some dedifferentiated and plemorphi liposarcomas to “malignat fibrous histocytoma” was sufficient to deny the specificity of the histologic pattern of the latter.

title: Myxoid liposarcoma--the frequency and the natural history of nonpulmonary soft tissue metastases.
abstract: Myxoid liposarcomas (ML) make up the major subset of liposarcomas, which in most series represent the second or third most common type of soft tissue sarcoma. The tendency for ML to metastasize to other soft tissues (STM) in preference to lung parenchyma has been previously described; however, the natural history of this tumor's behavior is poorly documented. Our intent was to analyze the natural history of ML and further quantify the incidence of STM, concentrating on their significance in terms of survival.



We reviewed the experience at the Royal Marsden Hospital over a 10-year period, documenting the clinicopathological behavior of ML, including the frequency of STM.



There were 50 patients, with a median follow-up of 43 months. The actuarial 5-year soft tissue metastasis rate was 31%, and the most common sites of STM were the retroperitoneum, abdominal wall, and abdominal cavity. In those 12 patients who had STM there was a median interval of 23 months after original diagnosis to the time the first metastasis became apparent (range, 0-142 months). Median survival following first metastasis was 35 months; 6 of the 12 patients died between 6 and 50 months. Four patients who had STM remain disease free at 15 to 59 months after their first STM. Any round cell component of the ML was associated with a significantly greater chance of metastatic disease (P = .02). In this series, the overall 5-year and 7-year survival rates were 85% and 68%. Patients with STM had an 11 times greater chance of dying than those who did not.



ML usually is an indolent disease, but there is a subset of patients who develop STM and have a significantly worse prognosis. STM can occur years after the initial diagnosis and can be associated with medium-long-term survival after they occur. STM should be managed aggressively because of this.

title: Pleomorphic Liposarcoma: A Clinicopathologic Analysis Of 19 Cases
abstract: Pleomorphic liposarcoma is a variant of liposarcoma defined morphologically by the presence of pleomorphic lipoblasts. Because of its rarity, there are limited studies with long-term follow-up information. Nineteen pleomorphic liposarcomas were studied. Unequivocal pleomorphic lipoblasts were required for inclusion. In each case, the following features were noted: tumor site; tumor size; tumor depth; predominant histologic pattern (epithelioid or malignant fibrous histiocytoma [MFH]-like); extent of necrosis (absent, less than 15%, or at least 15%); mitotic counts; treatment and clinical follow-up. Patients were 11 females and 8 males, aged 33–87 years (mean, 64.5 y; median, 70 y). Tumors involved the extremities (13 patients: intramuscular in 10, subcutaneous in 2, depth unknown in 1), retroperitoneum (4 patients), mediastinum (1 patient), and paratesticular region (1 patient). Size ranged from 4.5–31 cm (mean, 11.9 cm; median, 12.0 cm). Predominant pattern was epithelioid in 7 and MFH-like in 12. Necrosis was present in 15 (79%) and was extensive (36 15%) in 14 patients. Mitotic counts ranged from 0.2–3.4/10 high-power fields (mean, 1.4; median, 1.4) by the average-count method and from 1–6/10 high power fields by the highest count method (mean, 2.9; median, 3.0). All patients were treated surgically; 10 patients received adjuvant chemotherapy and/or radiation therapy. On follow-up of 18 patients (range, 2–129 mo; mean, 35.4 mo; median, 23 mo) nine (50%) were dead of disease (range, 2–48 mo; mean, 20.1 mo; median, 12 mo), one died of other causes 2 months after diagnosis, two were alive with disease, five were disease free, and one was alive at 129 months (tumor status unknown). Five had recurrences (range, 3–28 mo; mean, 14.4 mo; median, 8 mo), and four of five (80%) with recurrences were dead of disease. Metastases developed in eight patients (range, 4–48 mo; mean, 19.5 mo; median, 11.5 mo), most commonly to the lungs. In conclusion, pleomorphic liposarcoma is a rare tumor of adulthood that occurs most commonly in the deep, soft tissues of the extremities. It behaves as a high-grade sarcoma that frequently metastasizes, most commonly to the lungs. Although this tumor has a wide range of histologic appearances, no clinical or pathologic feature is predictive of a more aggressive clinical course.

title: Dedifferentiated liposarcoma: a clinicopathological analysis of 155 cases with a proposal for an expanded definition of dedifferentiation.
abstract: We studied 155 cases of dedifferentiated liposarcoma to define its clinicopathologic features and behavior, in particular how the extent and grade of dedifferentiation affected outcome. Tumors occurred in late adult life (median, 61.5 years: range, 21-92 years), most commonly in the retroperitoneum (106 cases), extremities and trunk (32 cases), and scrotum/spermatic cord (13 cases). The majority of dedifferentiated liposarcomas presented as de novo lesions, whereas the remainder developed as a late complication of a preexisting well-differentiated liposarcoma after an average interval of 7.7 years. At the time of presentation, most of the dedifferentiated liposarcomas displayed extensive areas of high-grade dedifferentiation resembling malignant fibrous histiocytoma or high-grade fibrosarcoma, whereas a minority contained only areas of low-grade dedifferentiation resembling fibromatosis or well-differentiated fibrosarcoma. Divergent myosarcomatous or osteosarcomatous differentiation was observed focally in six cases. The behavior of dedifferentiated liposarcomas was that of a high-grade sarcoma with a local recurrence rate of 41%, a metastatic rate of 17%, and disease-related mortality of 28%. The most important prognostic factor was location in that retroperitoneal tumors had significantly worse survival than those in other sites. Tumors were divided into those having less than or those with more than 25% dedifferentiation, and dedifferentiated zones were classified into low grade or high grade. Neither low-grade dedifferentiation nor a low percentage of dedifferentiation was associated with an improved outcome for the tumors examined in this study; however, in no cases was the absolute size of the dedifferentiated focus <2 cm. Therefore, this study did not determine a minimum, or threshold, amount of dedifferentiation below which outcome was more favorable. The behavior of liposarcomas in which the dedifferentiated component was entirely low grade was more similar to that of traditional dedifferentiated liposarcoma than to that of well-dedifferentiated liposarcoma. Our study supports the expansion of the definition of dedifferentiated liposarcoma to include tumors with low-grade dedifferentiation and also suggests that low-grade dedifferentiation represents a precursor lesion of high-grade dedifferentiation.

title: Atypical lipomatous tumor/well-differentiated liposarcoma of the extremity and trunk wall: Importance of histological subtype with treatment recommendations
abstract: BackgroundThis study defines the behavior and classification of atypical lipomatous tumors (ALT) and well-differentiated liposarcomas (WDLS) of the extremity and trunk. total of 91 well-differentiated lipomatous tumors of the extremity and trunk were identified from a soft tissue tumor database between July 1982 and June 2001. A soft tissue pathologist, blinded to prior diagnosis and clinical outcome, reviewed histology. Those composed predominantly of mature adipose tissue with scattered atypical stromal cells and scant lipoblasts or fibrosis were ALTs. Tumors with lipoblast but <25% fibrosis were termed lipoma-like WDLS, and those with >-25% fibrosis were identified as sclerosing WDLS. Clinical factors were analyzed to assess effects on local recurrence-free survival (LRFS).ResultsHistological review identified 34 ALTs and 57 WDLSs. Of the WDLSs, 29 were lipoma-like and 28 were sclerosing. Five-year and 10-year LRFS were 100%±0% and 78%±9%, respectively. Factors evaluated were age, sex, tumor site, tumor size, histology, presentation status, margin status, and adjuvant radiotherapy. Positive resection margins and sclerosing histology were associated with reduced LRFS. Dedifferentiation was observed in three tumors (3%)ConclusionsLipoma-like WDLSs and ALTs share similar histological features and favorable behavior. Margin-positive sclerosing WDLSs have a 10-year LRFS of only 17% and should undergo function-preserving re-excision when possible, or adjuvant radiotherapy.

title: Unusual manifestations of metastatic tumors to the lungs.
abstract: Because of the lung's rich capillary bed and central location in the circulatory system, this organ is one of the most frequent recipient sites for metastatic spread of disease. The histopathologic diagnosis in the vast majority of cases is straightforward and usually supported by clinical findings and a prior history of a known primary tumor elsewhere. However, unusual circumstances may arise: a primary tumor may remain occult at the time of pulmonary metastases, the metastasis may develop after a long period of latency, or the histopathologic appearance of the metastasis may assume a form that is uncharacteristic or inconsistent with the suspected primary lesion, which raises the possibility of the emergence of a second primary tumor in the lung. Herein we review a variety of unusual manifestations of metastatic disease to the lungs that may pose difficulties for diagnosis and interpretation. Emphasis is made on the histological differential diagnosis and the clues that may alert the pathologist to recognizing the process as metastatic in origin.

title: Pulmonary metastases from soft tissue sarcoma: analysis of patterns of diseases and postmetastasis survival.
abstract: To report the patterns of disease and postmetastasis survival for patients with pulmonary metastases from soft tissue sarcoma in a large group of patients treated at a single institution. Clinical factors that influence postmetastasis survival are analyzed.



For patients with soft tissue sarcoma, the lungs are the most common site of metastatic disease. Although pulmonary metastases most commonly arise from primary tumors in the extremities, they may arise from almost any primary site or histology. To date, resection of disease has been the only effective therapy for metastatic sarcoma.



From July 1982 to February 1997, 3149 adult patients with soft tissue sarcoma were admitted and treated at Memorial Sloan-Kettering Cancer Center. During this interval, 719 patients either developed or presented with lung metastases. Patients were treated with resection of metastatic disease whenever possible. Disease-specific survival was the endpoint of the study. Time to death was modeled using the method of Kaplan and Meier. The association of factors to time-to-event endpoints was analyzed using the log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis.



The overall median survival from diagnosis of pulmonary metastasis for all patients was 15 months. The 3-year actuarial survival rate was 25%. The ability to resect all metastatic disease completely was the most important prognostic factor for survival. Patients treated with complete resection had a median survival of 33 months and a 3-year actuarial survival rate of 46%. For patients treated with nonoperative therapy, the median survival was 11 months. A disease-free interval of more than 12 months before the development of metastases was also a favorable prognostic factor. Unfavorable factors included the histologic variants of liposarcoma and malignant peripheral nerve tumors and patient age older than 50 years at the time of treatment of metastasis.



Resection of metastatic disease is the single most important factor that determines outcome in these patients. Long-term survival is possible in selected patients, particularly when recurrent pulmonary disease is resected. Surgical excision should remain the treatment of choice for metastases of soft tissue sarcoma to the lung.

title: Pathology and genetics of tumours of soft tissue and bone
abstract: 1. Adipocytic tumours 2. Fibroblastic/Myofibroblastic tumours 3. So-called fibrohistiocytic tumours 4. Smooth muscle tumours 5. Pericytic (perivascular) tumours 6. Skeletal muscle tumours 7. Vascular tumours 8. Chondro-osseous tumours 9. Tumours of uncertain differentiation Bone Tumours 10. Cartilage tumours 11. Osteogenic tumours 12. Fibrogenic tumours 13. Fibrohystiocytic tumours 14. Ewing sarcoma/Primitive neuroedtodermal tumour 15. Haematopoietic tumours 16. Giant cell tumours 17. Notochordal tumours 18. Vascular tumours 19. Myogenic, lipogenic, neural and epithelial tumours 20. Tumours of undefined neoplastic nature 21. Congenital and inherited syndromes

title: The Normal Lung: The Basis for Diagnosis and Treatment of Pulmonary Disease
abstract: respiratory muscle function, assessment, and disease states. The book contains many other chapters dealing with topics of more limited and focused interest, such as "Evolution of the Mammalian Chest Wall," "Gravity, Immersion, Diving, and Chest Strapping," and "The Chest Wall and Respiratory Muscles in Obesity, Pregnancy and Ascites." The quality of the writing and the impartiality of the authors vary somewhat from chapter to chapter, and, as might be expected in a book with 61 contributors, the integration of material is not always ideal. In general, however, the overall quality and balance are excellent. I wholeheartedly recommend this outstanding reference source for respiratory physiologists, anesthesiologists, pulmonologists, and critical-care physicians. It may provide either a good basic understanding of the topics addressed or direction for further reading from the excellent bibliographies.

title: Analysis of 945 cases of pulmonary metastatic melanoma.
abstract: From 1970 to 1990, 7564 patients with melanoma were seen at Duke University Cancer Center. Complete follow-up data were available in all patients. The estimated probability of a pulmonary metastasis developing 5, 10, or 20 years after initial diagnosis was 0.13, 0.19, and 0.30, respectively. Pulmonary metastases were documented in 945 patients (12%), these having 1-, 3-, and 5-year survival rates of 30%, 9%, and 4%, respectively. The methods of diagnosis were chest radiograph (n = 544), computed tomography (n = 157), transthoracic needle biopsy (n = 121), bronchoscopy (n = 14), thoracotomy (n = 112), and autopsy (n = 7). Evidence of advanced pulmonic spread included bilateral disease in 543 and more than two nodules in 595. Univariate predictors for early formation of pulmonary metastases (p less than 0.001) were male sex, black race, increased primary thickness (millimeters), higher Clark's level, nodular or acral lentiginous histology, location on trunk or head and neck, and regional lymph nodes positive for metastasis. Multivariate predictors of improved survival (p less than 0.001) in order of importance were complete resection of pulmonary disease, longer time for formation of metastases, treatment with chemotherapy, one or two pulmonary nodules, lymph nodes negative for metastasis lymph nodes (p less than 0.005), and histologic type (p less than 0.04). Additionally, survival in patients with one nodule and resection (n = 84) was better than in those with similar disease and no resection (n = 142 months, p less than 0.001). These data comprise the largest series to date and emphasize the importance of long-term follow-up, as well as supporting the selective use of resection for isolated pulmonary metastases, increasing the 5-year survival rate from 4% to 20%.

title: Myxoid/round cell liposarcoma of the extremities. A clinicopathologic study of 29 cases with particular attention to extent of round cell liposarcoma.
abstract: Round cell liposarcoma, a high-grade sarcoma, is a poorly differentiated form of myxoid liposarcoma, which is low grade. It is not known, however, how much of a round cell component within an otherwise typical myxoid liposarcoma results in a neoplasm that behaves as a high-grade sarcoma. Twenty-nine cases of myxoid liposarcoma of the extremities with or without a component of round cell liposarcoma were studied to semiquantitate the amount of round cell component needed to adversely affect prognosis. An estimate of the percent of necrosis, round cell liposarcoma, myxoid liposarcoma, and transitional areas was obtained for each slide on all cases. Transitional areas were defined as those that displayed an increased cellularity compared with typical myxoid liposarcoma, but in which the cells remained spindled, did not have overlapping nuclear borders, and retained an easily discernible plexiform vascular pattern. The amount of necrosis was subtracted from the total material available for evaluation, and a composite estimate of the percent of round cell, myxoid, and transitional areas was obtained. Two tumors were located on the upper extremity, 27 on the lower extremity; tumor size ranged frm 3 to 30 cm (median, 14 cm). All 29 tumors had a myxoid component, with a range from 12 to 100% (median, 73%). The range of transitional component for all 29 tumors was 0 to 88% (median, 11%). Twenty-one tumors had transitional areas (range, 4-88%). The range of round cell component for all 29 tumors was 0 to 58% (median, 0%). Twelve tumors had round cell areas (range, 1-58%). Seventeen patients are either alive without disease, or died from unrelated causes at 24-202 months (median, 96 months). Twelve patients are either alive with metastases or died of disease at 10 to 180 months (median, 53 months). Patients with > 5% round cell component in their initial tumor had a statistically significant higher rate of metastasis or death due to disease than those with < or = 5% round cell liposarcoma (p = 0.05). In addition, patients with myxoid liposarcoma with transitional areas did not fare worse than those with myxoid liposarcoma alone. In conclusion, we found that a round cell component of > 5% portends a higher risk of metastasis or death from disease. Furthermore, transitional areas alone do not appear to alter the prognosis of myxoid liposarcoma. Thus, only those areas that are unequivocally round cell liposarcoma should be designated as high grade.

title: The clinicopathologic spectrum of myxoid and round cell liposarcoma: A study of 95 cases
abstract: The prognosis of patients with myxoid liposarcoma (ML) or round cell liposarcoma (RCL) has never been adequately defined.

title: Histologic Subtype and Margin of Resection Predict Pattern of Recurrence and Survival for Retroperitoneal Liposarcoma
abstract: The aim of this study was to determine the pattern of recurrence and prognostic significance of histologic subtype in a large series of patients with primary retroperitoneal liposarcoma.  Classification of liposarcoma into subtypes, based on morphologic features and cytogenetic aberrations, is now widely accepted. Previous studies have shown that high histologic grade and incomplete gross resection are the most important prognostic factors for survival in patients with retroperitoneal sarcoma and suggest that patients with liposarcoma have a 3-fold higher risk of local recurrence compared with other histologies.  A prospective database was used to identify 177 patients with primary retroperitoneal liposarcoma treated between July 1982 and June 2002. Histology at primary presentation was reviewed by a sarcoma pathologist and subtyped into 4 distinct groups according to strict criteria. The influence of clinicopathological factors on local recurrence, distant recurrence, and disease-specific survival was analyzed.  Of 177 patients with primary retroperitoneal liposarcoma operated on for curative intent, 99 (56%) presented with well-differentiated, 65 (37%) with dedifferentiated, 9 (5%) with myxoid, and 4 (2%) with round cell morphology. The tumor burden was determined by the sum of the maximum tumor diameters. The median tumor burden was 26 cm (5–139). Median follow-up time for 92 (52%) surviving patients was 37 (mean, 0.5–192) months. Multivariate analysis showed that dedifferentiated liposarcoma subtype was associated with a 6-fold increased risk of death compared with well-differentiated histology (P < 0.0001). In addition to histologic subtype, incomplete resection (P < 0.0001), contiguous organ resection (excluding nephrectomy; P = 0.05), and age (P = 0.03) were important independent prognostic factors for survival in retroperitoneal liposarcoma. Retroperitoneal dedifferentiated liposarcoma was associated with an 83% local recurrence rate and 30% distant recurrence rate at 3 years.  The histologic subtype and margin of resection are prognostic for survival in primary retroperitoneal liposarcoma. Dedifferentiated histologic subtype and the need for contiguous organ resection (excluding nephrectomy) was associated with an increase risk of local and distant recurrence. Nephrectomy may be needed to achieve complete resection, but has no measurable influence on disease specific survival.

title: The role of pulmonary metastasectomy in soft tissue sarcoma.
abstract: Pulmonary metastases are common in patients with soft tissue sarcoma. The majority of patients who develop pulmonary metastases are asymptomatic and are diagnosed during routine follow-up visits. There is evidence to suggest that pulmonary metastasectomy is associated with improved overall survival but only in patients with complete surgical resection. There are several criterion to identify patients for resection. The majority of resectable patients have peripheral lesions that are amenable to wedge resection. There is little evidence to suggest that chemotherapy improves survival. Future research is needed to better identify patients for metastasectomy, to determine the role of minimally invasive procedures, and to develop better adjuvant therapy.

title: Multifactorial analysis of the survival of patients with distant metastasis arising from primary extremity sarcoma
abstract: Despite optimal multimodality limb‐sparing therapy for extremity soft tissue sarcoma (STS), a significant number of patients develop distant metastasis. The objective of this study was to analyze patterns of metastatic disease and define prognostic factors for survival in a large group of patients followed prospectively at a single institution.

title: Pathology and Genetics of Tumours of Soft Tissue and Bone
abstract: Preparing the books to read every day is enjoyable for many people. However, there are still many people who also don't like reading. This is a problem. But, when you can support others to start reading, it will be better. One of the books that can be recommended for new readers is pathology and genetics of tumours of soft tissue and bone iarc who classification of tumours. This book is not kind of difficult book to read. It can be read and understand by the new readers.

title: Pulmonary epithelioid hemangioendothelioma with prominent signet ring cell features mimicking metastatic adenocarcinoma.
abstract: We report the case of a 65-year-old woman who presented with persistent dry cough and was initially treated for pneumonia without much improvement. Computed tomography of the chest showed a 2.5 cm poorly marginated right infrahilar opacity and multiple ill-defined ground glass opacities scattered throughout the lungs. Computed tomography-guided fine needle aspiration of the right infrahilarmass showed malignant epithelioid cells, many of which were strikingly plasmacytoid with a vacuolated cytoplasm suggesting signet ring cells. A diagnosis of adenocarcinoma with signet ring cell features was made and, in view of the clinical history of multiple masses in the lung, metastatic adenocarcinoma from sites such as gastrointestinal or pancreaticobiliary tract was favored. The patient underwent exploratory thoracotomy during which she was found to have multiple, small pulmonary nodules, one of which was sampled for intraoperative examination. Frozen section of the nodule was interpreted as adenocarcinoma with signet ring cell features, probably metastatic in origin. Histopathologic examination of the pulmonary nodules demonstrated fairly well-delineated lesions with an acellular central zone of hyalinized matrix surrounded by a more cellular zone of moderately pleomorphic epithelioid cells, some of which had a peripherally displaced nucleus and vacuolated cytoplasm resembling signet ring cells. The epithelioid cells were positive for vascular markers CD31 and CD34 and, therefore, a diagnosis of epithelioid hemangioendothelioma was confirmed. This case clearly indicates the importance of recognizing the cytomorphologic and histologic spectrum of this entity to avoid misdiagnosing it as either primary or metastatic adenocarcinoma.

title: Epithelioid variant of pleomorphic liposarcoma: a study of 12 cases of a distinctive variant of high-grade liposarcoma.
abstract: We describe 12 patients with a distinctive variant of pleomorphic liposarcoma that histologically shows epithelioid features and focally resembles a solid carcinoma. The tumors occurred in nine men and three women (median age, 63 yr; range, 40-78 yr). Five tumors were in the thigh, two in the chest wall, two in the axilla, and one each in the retroperitoneum, groin, and calf. Most were 15 to 20 cm in maximal diameter. They consisted of sheets of epithelioid-appearing cells with ample, variably eosinophilic cytoplasm, often showing a honeycomb-like pattern of cell borders and little if any collagenous extracellular matrix. Their histologic features often resembled those of renal clear cell carcinoma or adrenal cortical carcinoma, but all showed evidence of adipocytic differentiation, and five also showed focal spindle cell components. One patient whose tumor in the thigh had been originally diagnosed as metastatic renal carcinoma had undergone nephrectomy without a finding of a kidney tumor. All of the cases were positive for vimentin; 6 of 11 cases were positive for S-100 protein, usually focally; 5 of 11 were focally positive for keratins; and all were negative for epithelial membrane antigen, muscle actins, desmin, and CD34. High mitotic activity (mean, 42 mitotic figures per 10 high power fields) and high MIB-1-positive proliferative fraction (>30%) were seen in all of the cases, and nuclear p53 immunoreactivity was detected in five of seven cases. Of the eight patients with complete follow-up, five died of disease (median survival, 6 mo), two died of unrelated causes 10 and 18 years later, and 1 was alive and well 24 years later. The epithelioid variant of pleomorphic liposarcoma is a high-grade tumor that must be distinguished from malignant epithelial tumors, especially in view of the keratin immunoreactivity of some of these neoplasms.

title: Malignant epithelioid vascular tumors of the pleura: report of a series and literature review.
abstract: Primary malignant vascular tumors of the pleura are rare. The significance and difficulty of distinction between pleural epithelioid hemangioendothelioma (EHE) and angiosarcoma have not yet been addressed. A new series of pleural angiosarcoma is reported, and the relevant literature is reviewed. Five cases were identified from files of the authors' institutions and personal consultation cases (J.J.B.). Twenty-six cases of primary malignant vascular tumors of the pleura were identified in the literature. In a total of 31 cases, 22 were from the West and 9 from Japan. Patients were 22 to 79 years old (average, 57), and the male/female ratio was 9:1. Prior chronic pyothorax was identified only in cases reported from Japan. History of exposure to radiation or asbestos was noted in a few Western cases. The most common presentation was pleural thickening and effusion. Almost all of the patients died of disease shortly after diagnosis. A spectrum of histology ranging from characteristic high-grade epithelioid to relatively low-grade EHE-like features was observed in our cases and can be found in previous reports. Most cases showed variable spotty cytokeratin immunoreactivity. Endothelial markers (factor 8, CD34, or CD31) were invariably positive. Pleural angiosarcomas are often epithelioid and can be easily mistaken for mesothelioma or carcinoma clinically and histologically. Awareness of this rare tumor should prompt the use of endothelial markers when faced with a questionable mesothelioma. When cytokeratin is negative, or focal with strong vimentin reactivity, a vascular tumor should be suspected and confirmed with vascular markers. Because of their invariably aggressive behavior, all epithelioid vascular tumors of the pleura should be considered highly malignant regardless of the presence of EHE-like histological features.

title: The association between tumour progression and vascularity in myxofibrosarcoma and myxoid/round cell liposarcoma
abstract: Angiogenesis is an important factor in the morphological progression and metastasis of many solid tumours. We studied two homogeneous series of myxofibrosarcoma (MFS) and myxoid/round liposarcoma (MRLS), characterised by distinct vascular patterns and correlated the intratumoral microvessel density (IMD) with morphologic progression in both types of sarcoma. In our study, 43 cases of MFS and 42 cases of MRLS were graded according to established diagnostic criteria. For evaluation of IMD, representative sections were stained immunohistochemically for CD31. After selection of "neovascular hot spots", IMD was calculated by measuring the endothelial surface within twenty 200× fields in relation to the total analysed area. In addition to the correlation of IMD with histological grades of malignancy, a correlation of IMD with the inflammatory infiltrate in MFS was done. To determine whether vascular endothelial growth factor (VEGF) and its receptors, KDR and flt-1, may play a role in the progression of both types of sarcomas, we used mRNA in situ hybridisation (ISH) to study VEGF, KDR and flt-1 expression in selected cases. In addition, the expression of thrombospondin-1, which has been reported to inhibit angiogenesis, and of collagen type  I was studied using mRNA ISH. Cases of MFS varied histologically from hypocellular, mainly myxoid, neoplasms (low-grade malignant, 18 cases) to intermediate-grade malignant lesions with increased cellularity and mitotic activity (13 cases), and high-grade malignant cases with marked pleomorphism, high proliferative activity and areas of necrosis in many cases (12 cases). Cases of purely low-grade myxoid liposarcoma (16 cases) were characterised by low-cellularity, mucin pooling and plexiform vasculature. In combined MRLS, these hypocellular areas were admixed with hypercellular, round cell areas (5–80% of the analysed tumour area; 23 cases), and in round cell liposarcoma (three cases) rounded tumour cells predominated (>80% of the analysed tumour area). The average IMD in intermediate and high-grade malignant MFS (4.03 and 4.09, respectively) was significantly higher than in low-grade malignant MFS (2.73). Correlation of vascularity with the inflammatory infiltrate in MFS showed increased IMD only in cases with abundant neutrophils; most of these cases were high-grade malignant neoplasms. In contrast, no statistical correlation between morphological progression and IMD was seen in myxoid liposarcoma (6.08), MRLS (6.57) and round cell liposarcoma (4.07). VEGF mRNA was expressed by tumour cells in all histological grades of MFS and MRLS. VEGF receptor mRNA was weakly expressed by endothelia of newly formed blood vessels in both entities. Interestingly, tumour cells of all analysed cases of MFS strongly expressed collagen type I and thrombospondin-1, while these proteins were not detected in tumour cells of MRLS. In conclusion, morphologic tumour progression in MFS is associated with increased IMD, whereas, in MRLS, no such correlation is seen. Whereas VEGF and VEGF receptor mRNA were expressed in both entities, a characteristic expression profile of collagen type I and thrombospondin-1 in MFS emerged. Further studies are necessary to correlate vascularity and clinical course in MFS and MRLS.

title: Cytogenetic findings in liposarcoma correlate with histopathologic subtypes
abstract: The cytogenetic findings in 31 liposarcomas from 26 patients are reported. Four other tumors did not grow. Three histologic types are represented in this analysis. The well‐differentiated liposarcomas were characterized by telomeric associations, large marker chromosomes and ring chromosomes, and in some cases, double minutes. The pleomorphic liposarcomas contained very high clonal chromosomal numbers with near‐tetraploid modes and numerous variable, often unidentifiable, chromosomal abnormalities. The myxoid liposarcomas were characterized primarily by a t(12;16)(q13;pll) as the sole abnormality or additional changes. These results indicate that cytogenetic findings may provide a new criterion, not only for establishing the diagnosis of liposarcoma, but also for differentiating confusing histologic types of liposarcoma and these lesions from other types of sarcomas. Cancer 1992; 69:2484‐2495.

title: The genetics of lipomatous tumors.
abstract: The current classification of lipomatous neoplasms has been validated by the identification of characteristic cytogenetic and molecular genetic profiles associated with various neoplasms within the family of lipomatous tumors. The review describes characteristic cytogenetic and molecular genetic profiles and discusses their significance. The clinicopathologic features of these tumors, which are described elsewhere, will not be included in this review.

title: Pleomorphic Liposarcoma: Clinicopathologic, Immunohistochemical, and Follow-up Analysis of 63 Cases: A Study From the French Federation of Cancer Centers Sarcoma Group
abstract: The clinicopathologic and immunohistochemical features of 63 pleomorphic liposarcomas are presented. There were 35 men and 28 women (median age 63 years; range 18–93 years). Tumor size ranged from 2 to 23 cm (median 10 cm). Tumor locations included lower extremity (36.5%), especially the thigh (28.5%), limb girdles (17.5%), upper extremity (16%), thoracoabdominal wall (9.5%), and internal trunk (20.5%). A total of 75% were deep seated and/or extracompartmental. Histologically, lesions show a varying combination of lipogenic and nonlipogenic areas characterized by malignant fibrous histiocytoma-like, round cell liposarcoma-like, and/or epithelioid/carcinoma-like features. A pericytic pattern was focally present in 15 (24%) tumors. Eighteen (29%) lesions were grade 2, and 45 (71%) were grade 3 sarcomas. Tumor necrosis was observed in 51 (81%) cases, vascular invasion in three, and mitotic counts ranged from 3 to 124 per 10 high power fields (median 25). Lipogenic areas were S-100 protein immunoreactive, at least focally, in 20 of 42 (48%) cases. Nonlipogenic areas showed focal reactivity for smooth muscle actin (24 of 49; 49%), desmin (9 of 48; 19%), CD34 (18 of 45; 40%), S-100 protein (5 of 49, 10%), CD68 (6 of 46, 13%), and epithelial membrane antigen (13 of 49, 26.5%). Epithelioid areas showed epithelial membrane antigen (4 of 11; 36%) but not cytokeratin (0 of 11) reactivity. Treatment procedures in 51 patients consisted of simple tumorectomy (16) and wide excision (33). Five and 31 patients received neoadjuvant and adjuvant chemotherapy and/or radiation therapy, respectively. Follow-up (48 patients, range 7–276 months; median 38 months) showed a 45% local recurrence rate and a 42.5% metastasis rate, metastases occurring mostly in lungs and pleura. Seventeen patients (35%) died of disease, of whom none was metastatic at diagnosis. Five-year overall, metastasis-free, and local recurrence-free survivals were 57%, 50%, and 48%, respectively. Patient age ≥60 years, truncal tumor location, deep situation, tumor size >5 cm, vascular invasion, and incomplete tumor excision were significant adverse prognostic factors. Tumor grade and histology did not affect patient outcome. In conclusion, pleomorphic liposarcoma is a rare, often deep-seated and limb-based aggressive and metastasizing neoplasm of late adulthood. It shows a wide range of morphologic appearances, but tumor grade and histology have no effect on patient outcome.

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

title: Distinct chromosomal imbalances in pleomorphic and in high‐grade dedifferentiated liposarcomas
abstract: Using comparative genomic hybridization, DNA copy number changes were studied in 14 pleomorphic liposarcomas and compared to those detected in high‐grade areas of 9 dedifferentiated liposarcomas. A total of 251 gains and 84 losses were detected. The most frequent gains involved subregions of chromosomal arms 12q and 20q (70% each), 5p (57%), 6q and 9q (52% each), 1q, 7p and 17p (48% each), 1p (43%), 6p and 17q (39% each), 20p and 22q (35% each) as well as 7q and 12p (30% each). The same subregions were also affected by 30 high level amplifications. The most frequent losses were found in subregions of chromosomal arms 13q (35%) as well as 11q and 12p (30% each). Overall, gains of chromosomal material were more frequent than losses (p < 0.001). There were significant differences in the frequency and distribution of recurrent chromosomal imbalances between pleomorphic liposarcomas and the dedifferentiated areas of dedifferentiated liposarcomas. Gains of chromosomal material detected predominantly in pleomorphic liposarcomas involved subbands 5p13–p15 (p < 0.010), 1p21 (p < 0.019), 1q21–q22 (p < 0.040) and 7q22 (p < 0.049). Conversely, high level amplifications within chromosomal subregion 12q13–q21 were only found in the dedifferentiated components of dedifferentiated liposarcomas (p < 0.001). Overall, both gains and the less pronounced losses of chromosomal material were more frequent in pleomorphic than in dedifferentiated liposarcomas (p < 0.001 and p < 0.025, respectively). These results show that pleomorphic liposarcomas display a considerable number of recurrent chromosomal imbalances that are essentially different from those present in high‐grade areas of dedifferentiated liposarcomas. Therefore, genetic data are considered as a helpful diagnostic adjunct for the discrimination between these 2 types of liposarcoma. The overall higher frequency of chromosomal imbalances in pleomorphic as compared to dedifferentiated liposarcomas could account for the more aggressive biological behavior of pleomorphic relative to dedifferentiated liposarcoma types.

title: Dedifferentiated Liposarcoma Clinicopathologic Analysis of 32 Cases Suggesting a Better Prognostic Subgroup Among Pleomorphic Sarcomas
abstract: Dedifferentiated liposarcoma is uncommon, and only a small number of cases have been documented. We describe the clinicopathologic features in a series of 32 cases. All patients were adults (age range, 37–83 years; median, 67 years); 20 were men and 12 were women. Commonest site was the retroperitoneum (fifteen cases); six cases arose in the limbs, four in the paratesticular region, three in the peritoneal cavity, two on the trunk, and one each in the buttock and larynx. One primary tumor was subcutaneous. Thirty tumors arose de novo (i.e., combined with well-differentiated tumor in the primary lesion), while two developed in recurrences of a previously well-differentiated liposarcoma. The well-differentiated component was most often lipoma-like and typically there was a histologically abrupt transition to spindle celled nonlipogenic tumor. The dedifferentiated component most often resembled either storiform “malignant fibrous histiocytoma” (“MFH”) with limited pleomorphism or myxofibrosarcoma (myxoid “MFH”); the latter pattern is rarely otherwise seen in the retroperitoneum. A small number of cases showed appearances reminiscent of myxoid embryonal rhabdomyosarcoma. An unusual feature in three cases was the occurrence of a discontinuous micronodular pattern of dedifferentiation. Average follow-up of 5.6 years (range, 3 months to 33 years) in 27 cases have revealed local recurrence in 14 patients and systemic metastases in only four patients. The primary sites of the metastasising cases were upper back, thigh, retroperitoneum, and paratesticular region. There have been only seven tumor-related deaths. Good prognosis in de novo dedifferentiated liposarcomas seems unrelated to the extent or morphologic pattern of dedifferentiation. However, high mitotic activity in the dedifferentiated component was associated with a more aggressive clinical course. Our study underlines that dedifferentiation in peripherally located or even subcutaneous liposarcomas does occur, albeit rarely, and that dedifferentiated liposarcomas of the limbs may metastasize. The results suggest that dedifferentiated liposarcomas, as a subgroup among the “MFH-like” sarcomas, have a better prognosis than pleomorphic sarcomas as a whole.

title: Epithelioid hemangioendothelioma a vascular tumor often mistaken for a carcinoma
abstract: Epithelioid hemangioendothelioma is a unique tumor of adult life which is characterized by an “epithelioid” or “histiocytoid” endothelial cell. Forty‐one cases of this rare tumor have been recognized at the Armed Forces Institute of Pathology. They may occur in either superficial or deep soft tissue, and in 26 cases appeared to arise from a vessel, usually a medium‐sized or large vein. They are composed of rounded or slightly spindled eosinophilic endothelial cells with rounded nuclei and prominent cytoplasmic vacuolization. The latter feature probably represents primitive lumen formation by a single cell. The cells grow in small nests or cords and only focally line well‐formed vascular channels. The pattern of solid growth and the epithelioid appearance of the endothelium frequently leads to the mistaken diagnosis of metastatic carcinoma. The tumor can be distinguished from a carcinoma by the lack of pleomorphism and mitotic activity in most instances and by the presence of focal vascular channels. Ultrastructural study in four cases confirmed the endothelial nature of the tumor in demonstrating cells surrounded by basal lamina, dotted with surface pinocytotic vesicles, and occassionally containing Weibel‐Palade bodies. Follow‐up information in 31 cases indicated that 20 patients were alive and well following therapy; three developed local recurrences and six metastases. It is suggested the term epithelioid hemangioendothelioma be used to designate these biologically “borderline” neoplasms. The significance of the epithelioid endothelial cell is not entirely clear. Since it may be observed in both benign and malignant vascular lesions, its presence alone does not define a clinicopathologic entity.

title: Liposarcoma: new entities and evolving concepts.
abstract: Liposarcoma is the most common soft tissue sarcoma and accounts for approximately 20% of all mesenchymal malignancies. In the last decade, the results of several studies have led to the delineation of new variants as well as to the introduction of new concepts, mainly as a result of the fruitful interactions between genetics and pathology. Spindle cell liposarcoma represents an uncommon variant of well-differentiated liposarcoma. It tends to occur in adults and often involves the subcutaneous soft tissue. However, from the observation of a larger number of cases, the anatomic distribution of spindle cell liposarcoma seems to be comparable to that of the other well-differentiated liposarcoma subtypes. Spindle cell liposarcoma tends to recur locally and may dedifferentiate. Morphologically it is composed of a fairly bland neural-like spindle cell proliferation set in a fibrous and/or myxoid background and is associated with an atypical lipomatous component. Great debate has been generated by the introduction of the term atypical lipoma to emphasize the fact that well-differentiated liposarcoma shows risk of local recurrence but no potential for metastasis. In our opinion well-differentiated liposarcoma and atypical lipoma should be considered synonyms that describe lesions identical both morphologically and kayotypically. Dedifferentiated liposarcoma is a distinct type of liposarcoma in which transition from low-grade to high-grade nonlipogenic morphology within a well-differentiated liposarcoma is observed. The transition usually occurs in an abrupt fashion; however, in rare cases it can be more gradual. Recently, it also has been proposed that dedifferentiated liposarcoma should be further classified into low and high grade. Dedifferentiated liposarcoma rarely exhibits heterologous (most often myoid) differentiation. A peculiar "neural-like whorling pattern" of dedifferentiation also has been described recently. Surprisingly, the clinical outcome of dedifferentiated liposarcoma is less aggressive that in other high-grade pleomorphic sarcomas but genetic as well as molecular data exist that may partiallyjustify such a discrepancy. Myxoid and round cell liposarcoma, even if still classified by the World Health Organization as two distinct subtypes, share both clinical and morphologic features. Lesions combining both patterns are very frequent and wide agreement exists in considering round cell liposarcoma as the high-grade counterpart of myxoid liposarcoma. Furthermore, myxoid and round cell liposarcoma share the same characteristic chromosome change. Albeit rare, it has been recently shown that liposarcoma indeed can occur as a primary skin lesion. It often presents clinically as a dome-shaped or polypoid lesion that, histologically, most frequently shows high-grade morphologic features but carries a comparatively good prognosis. Considering currently available data, the most logical classification of liposarcoma is into three main groups: (1) well-differentiated liposarcoma (including adipocytic, sclerosing, inflammatory, spindle-cell, and dedifferentiated variants), characterized by ring or long markers chromosomes derived from the long arm of chromosome 12; (2) myxoid and round cell (poorly differentiated myxoid) liposarcoma, characterized in most cases by a reciprocal translocation t(12;16)(q13;p11); and (3) pleomorphic liposarcoma, characterized by complex karyotypes.