Liposarcoma
Liposarcomas are the most common subtype of soft tissue sarcomas, accounting for at least 20% of all sarcomas in adults. Soft tissue sarcomas are rare neoplasms with over 150 different histological subtypes or forms. Liposarcomas arise from the precursor lipoblasts of the adipocytes in adipose tissues. Adipose tissues are distributed throughout the body, including such sites as the deep and more superficial layers of subcutaneous tissues as well as in less surgically accessible sites like the retroperitoneum and visceral fat inside the abdominal cavity.
All liposarcomas consist of at least some cells that bear a resemblance to fat cells when examined for their histopathologic appearances under a microscope. However, the liposarcomas do have several forms based on differences in their clinical presentations, severities atypical lipomatous tumor/well-differentiated liposarcoma dedifferentiated liposarcoma myxoid liposarcoma; 4) pleomorphic liposarcoma; and 5)''' myxoid pleomorphic liposarcoma.
While liposarcoma forms are classified as being aggressive and malignant or, in the case of the atypical lipomatous tumor/well-differentiated liposarcoma, as relatively non-aggressive and benign, all five liposarcoma forms can infiltrate locally to injure nearby tissues and organs, occur in surgically inaccessible sites adjacent to vital organs, recur after surgical removal, and progress to life-threatening diseases. Studies to date find that all five liposarcoma forms, while usually treatable at least initially by surgical resection, are often only marginally responsive to currently used chemotherapy and radiotherapy regimens. The liposarcomas require a wide range of further studies to determine their responsiveness to various radiotherapy, chemotherapy, and more novel treatment regimens as used individually and in various combinations that would include, where possible, surgical removal.Etymology
"fatty tumor", 1830, medical Latin, from Greek lipos "fat", from PIE root *leip- "to stick, adhere", also used to form words for "fat", + -oma.
1650s, "fleshy excrescence",, Medical Latin, from Latinized form of Greek sarkoma "fleshy substance", from sarkoun "to produce flesh, grow fleshy", from sarx "flesh", + -oma.Forms of liposarcomas
Liposarcomas are generally large tumors but can be of almost any size. They occur mainly in adults with only 0.7% of cases occurring in those <16 years old. In adults, liposarcomas occur predominantly in and after middle-age. The very rare cases occurring in children and adolescents are diagnosed predominantly as being the myxoid liposarcoma form.
The five liposarcoma forms must be distinguished not only from each other but also from certain other soft tissue tumors. These other tumors along with some of their distinguishing histopathologic features are: 1) dysplastic lipomas atypical spindle cell lipomas pleomorphic lipomas ''' solitary fibrous tumors.Atypical lipomatous tumor/well-differentiated liposarcoma
Together, atypical lipomatous tumors and well-differentiated liposarcomas account for 4045% of all liposarcomas. They rarely if ever metastasize and therefore are regarded as benign or premalignant tumors. However, they are locally invasive and may transform to a more aggressive and potentially metastasizing liposarcoma, i.e. a dedifferentiated liposarcoma. Furthermore, a surgically removed atypical lipomatous tumor/well-differentiated liposarcoma may recur as a dedifferentiated liposarcoma.Presentation
ALTs and WDLs are considered virtually identical tumors except that by definition ALTs designate tumors that develop in the arms or legs while WDLs designate tumors that develop in less surgically accessible sites such as the deep, centrally located soft tissues of the retroperitoneum, paratesticular region, oral cavity, and eye socket. This terminology has prognostic implications: less than 7% of ALT tumors convert to dedifferentiated liposarcomas within a median time of 7 years while 17% of WDL tumors convert to this more malignant liposarcoma within a median time of 8 years. ALT and WDL tumors typically present in middle-aged and older individuals as slowly enlarging masses that tend to be larger and at a more advanced stage when located in deep tissues. These tumors usually are not painful and if located superficially, readily apparent; they can also cause extensive edema in involved areas such as the thigh due to their invasion into the blood and/or lymphatic vessels draining the tumor's site. Deep-seated ALT/WDL tumors may be asymptomatic but, depending on their location, produce serious signs and/or symptoms of disfunction in any one of the various organs which they infiltrate. These organs include those close to or in the retroperitoneum ; the paratesticular region; the mediastinum ; and the head.Pathology
Histopathologically, ALT/WDL tumors are divided into adipocytic/lipoma-like, sclerosing, and inflammatory variants with adipocyte/lipoma-like being the most common. Adipocytic/lipoma-like ALT/WDL tumors consist of lobules of mature fat cells variably intersected with irregular fibrous septa. Sclerosing ALT/WDL tumors, the second most common variant, develop primarily in the retroperitoneal and paratesticular areas; it consists of scattered, atypical stromal cells within a collagenous stromal tissue background. Rare vacuole-containing lipoblasts populate this tissue. Inflammatory ALT/WDL tumors are the rarest variant. they occur most frequently in the retroperitoneum and consists of chronic inflammatory cells, e.g. lymphocytes and plasma cells plus occasional lymph node-like follicles interspersed throughout a tissue background containing fat cells.Genetics
The neoplastic cells in ALT/WDL tumors contain one or more extra ring-shaped small supernumerary marker chromosome or an abnormal giant marker chromosome. These abnormal chromosomes contain extra copies of chromosome 12's long arm at bands 13 through 15. This stretch of chromosome 12 includes the MDM2 proto-oncogene located at band 15 and CDK4 located at band 14.1. The amplification of these two genes is a highly sensitive and specific indicator that a liposarcoma is either an ALT/WDL or a dedifferentiated liposarcoma rather than any other liposarcoma or lipoma form. In addition to the MDM2 and CDK4 genes, this band 13–15 chromosome area also contains the TSPAN31 and HMGA2 genes which, when overexpressed, are associated with various tumors and/or cancers. One or more of these overexpressed genes, it has been suggested, promote and/or contribute to the development and/or progression of ALT/WDL tumors.Diagnosis
The diagnosis of ALT/WDL tumors is made based on the features of their clinical presentations, histopathology, and genetic findings. In particular, detection in the ALT/WDL tumor cells of an overexpressed MDM2 or CDK4 gene or the presence of either the specific ALT/WDL-associated sSMC or giant marker chromosome strongly supports the diagnosis of ALT/WDL or dedifferentiated liposarcoma. The clinical presentation and histopathology differences between the latter two liposarcoma forms usually help distinguish between them.Treatment and prognosis
ALT/WDL tumors are treated by radical surgical resection to remove all tumor neoplastic tissues. However, these tumors recur locally in 30–50% of cases. Recurrences occur most often in tumors located in less accessible sites such those in the retroperitoneum, mediastinum, and spermatic cord. These less surgically assessible tumors tend to recur repeatedly and ultimately may cause death due to their injurious effects on vital organs. While ALT/WDL tumors have very little potential to metastasize, about 10% will convert to an overtly malignant and potentially metastasizing liposarcoma form, dedifferentiated liposarcoma. The median time for this malignant transformation is about 7–9 years. In addition, a surgically removed ALT/WDL may recur after a variable interval as a dedifferentiated liposarcoma. A large randomized controlled trial comparing radiotherapy followed by surgery to surgery alone in ALT/WDL tumors found little difference between the two regimens. Smaller studies employing selective inhibitors of the protein products of the CDK4 or MDM2 genes implicated in ALT/WDL have shown at best only modest effects. Further studies using these or completely novel treatment regimens are under investigation. A review study in 2012 reported the 5 and 10 year survival rates of individuals with ALT/WDL to be 100% and 87%, respectively.Novel therapies
The novel therapies of ALT/WDL are the same as those listed in the Novel therapies section of Dedifferentiated liposarcoma.Dedifferentiated liposarcoma
Dedifferentiated liposarcomas are malignant tumors which in ~10% of cases develop in an existing atypical lipomatous tumor/well-differentiated liposarcoma tumor or at the site were an ALT/WPL tumor was surgically removed. Individuals with a de novo diagnosis of this tumor may have had an ALT/WDL that progressed to a dedifferentiated liposarcoma but went undetected because it developed asymptomatically in a highly sequestered site such as the retroperitoneum or abdominal cavity. Many of the dedifferentiated liposarcoma tumors' clinical and genetic features are similar to those found in ALT/WDL tumors.Presentation
Dedifferentiated lipoosarcomas occur most frequently in middle-aged and older adults with a peak incidence in their sixth to eighth decades. Rarely, these tumors have developed in children and adolescents. DDL tumors most commonly occur in the retroperitoneal space but, similar to ALT/WDL, may occur in the extremities, paratesticular area, mediastinum, head, or neck. Less than 1% of all DDLs develop in superficial soft tissues or the eye socket. At presentation, DDL tumors typically are painless, large, may have been slowly and progressively enlarging for years, and on routine X-rays contain areas of calcium deposition. Less commonly, affected individuals have signs and/or symptoms due to their tumor's impingement on an organ. Very rarely, individuals with DDL present with one or more signs or symptoms of chronic inflammation and/or one of the endrocrine, neurological, mucocutaneous, hematological, or other tissue-related paraneoplastic syndromes. The signs and symptoms of chronic inflammation and the various paraneoplastic syndromes are caused by the tumors' secretion of cytokines, hormones, prostaglandins, and/or other systemically acting agents; they completely disappear after the DDL is successfully treated.