"Hey! Whatever happened to hemangiopericytoma and fibrosarcoma?" An update on selected conceptual advances in soft tissue pathology which have occurred over the past 50 years.

Hemangiopericytoma and fibrosarcoma represented at one time two of the most common diagnoses in soft tissue pathology. Both terms are now largely extinct. This article will review the clinicopathologic, immunohistochemical and molecular genetic advances that have led to these changes, and review the pathologic features of a select group of soft tissue tumors previously classified as hemangiopericytoma or fibrosarcoma.

Histology of ancient soft tissue tumors: A review.

Ancient neoplasms diagnosed in the soft tissues of mummies are limited to 18 cases so far, with only 5 malignant tumors. The apparent paucity of neoplasms in ancient populations is sometimes attributed to shorter life spans and fewer oncogenic substances in the environment. However, this paucity may also be a result of the scarcity of autopsies of mummies, together with technical difficulties in detecting neoplastic lesions in mummified tissues. An exception, and example of the benefits of thorough systematic analysis, is the small sample of 10 Renaissance mummies from Naples (15th-16th centuries), in which 3 cases of cancer were found. In order to increase detection of soft tissue tumors, it is imperative that mummies undergo systematic autopsies and histological examinations performed by skilled paleopathologists. This review of the known ancient soft tissue neoplasms demonstrates the state of histology of malignant and benign soft tissue neoplasms in mummies, and the potential for further study. The limitations of paleopathological diagnosis will be discussed and an argument will be made for the use of autopsies and histological analysis on mummified human remains.

Radiotherapy for soft tissue sarcoma: 50 years of change and improvement.

Radiotherapy for soft tissue sarcoma (STS) has advanced significantly over the past 50 years. This review focuses briefly on the period from 1964 to 1999 and more substantially on the changes of the past 15 years, such as IMRT and image-guided radiotherapy (IG-RT), especially when brought together (IG-IMRT) in the same planning and delivery process to treat localized STS. In particular, the introduction of IG-RT, target volume definitions for IG-RT, and review of recent clinical trials using IG-RT to treat localized STS in extremity will be reviewed. Finally, potential investigational agents combined with IG-RT to improve outcomes in patients with localized STS are discussed.

Surgical advances in bone and soft tissue sarcoma: 50 years of progress.

As the American Society of Clinical Oncology celebrates its 50th anniversary, physicians can appreciate the significant advances made in the treatment of patients with sarcoma. Historically, these rare tumors have garnered great interest in the medical profession, due to their ability to reach extraordinary size, resulting in substantial deformities and disabilities. Fortunately, advances in surgical management, which have occurred concurrently with advances in imaging, diagnostic techniques, and both local and systemic adjuvant treatments, offer patients diagnosed with sarcoma significant hope for successful treatment and the expectation of a meaningful quality of life.

Fifty years of advances in sarcoma treatment: moving the needle from conventional chemotherapy to targeted therapy.

Much of the progress in systemic therapy for sarcomas was accomplished in the first half of the last 5 decades. Various chemotherapeutic agents were tested in the 70s through the 80s and became part of the standard of care for this patient population. During the decade of the 90s, dose intensification became feasible as a result of improved supportive care and the availability of growth factors, thus maximizing the therapeutic potential of this class of agents. However, response rates and survival plateaued and it became obvious that newer and mechanistically different agents were needed to improve the therapeutic index and gain further enhancement of outcomes. Since early 2000, primarily inspired by the experience with imatinib in gastrointestinal stromal tumors (GISTs), several targeted therapies have been tested in sarcomas with modest success. The major limitations encountered include the lack of drivers and actionable targets for bone and soft tissue sarcomas with complex genomic profiles. Continued investigations and sequencing of larger numbers of these rare and heterogeneous malignancies could shed some light on a path toward improved outcomes.

Soft tissue tumors in palaeopathology: a review.

OBJECTIVE: To perform a review of soft tissue tumors in palaeopathology. METHODS: Examination of palaeopathological literature. RESULTS: Up to now, observations of neoplastic soft tissue lesions in mummified remains are limited to 15 cases, and only 4 of them present malignancies; 14 cases of calcified benign tumors, including 13 neoplasms of the female reproductive system and 1 teratoma, are also documented. CONCLUSIONS: The main reasons for the rarity of soft tissue tumors in palaeopathology, especially of malignancies, are apparently the short life span of past populations, the scarcity of mummified remains available in comparison with skeletal remains, and technical difficulties in the detection of neoplastic lesions in mummified tissues.

Lipomatous tumors-how we have reached our present views, what controversies remain and why we still face diagnostic problems: a tribute to Dr Franz Enzinger.

The group of soft tissue lipomatous tumors constitutes an unusually complex clinical and morphologic mosaic. Over the last 4 decades, there has been great progress in identifying recognizable and reproducible patterns that are of great clinical significance. Through his sharp eyes, analytical and scientific mind, and didactic skills, Dr Franz Enzinger has played a key role in this development. Recent genetic discoveries in the field of lipomatous tumors have confirmed morphologically based theories and provided new insight into pathogenetic mechanisms.

Clear cell sarcoma of tendons and aponeuroses: a historical perspective and tribute to the man behind the entity.

Clear cell sarcoma of tendons and aponeuroses is a unique sarcoma initially described by Dr Franz M. Enzinger. The tumor has a proclivity to involve the tendons and aponeuroses of distal extremities of relatively young individuals and is characterized by multiple local recurrences with late metastases and a high rate of tumor deaths. Since its seminal description in 1965, there have been many studies verifying the uniqueness of this entity and probing its differentiation. Ultrastructural and immunohistochemical studies have shown melanocytic differentiation, whereas molecular genetic studies have shown cytogenetic rearrangements resulting in a EWSR1-ATF1 fusion gene that is characteristic but not entirely unique for clear cell sarcoma (similar fusion genes are also seen in angiomatoid fibrous histiocytoma). Detection of this fusion gene and the absence of BRAF gene mutations clearly distinguish clear cell sarcoma from cutaneous melanoma. Adverse prognostic factors identified to date include larger tumor size and any microscopic tumor necrosis. Surgery is the mainstay of treatment for this high grade sarcoma, with chemotherapy having little effect. Although the melanocytic differentiation of clear cell sarcoma is indisputable, its precise lineage remains unclear. Thus, clear cell sarcoma maintains the status of a unique yet enigmatic clinicopathologic entity of ever increasing complexity 40 years after its original description by an extraordinarily gifted man.

Epithelioid sarcoma of Enzinger.

Epithelioid sarcoma was named in 1970 in a classic paper by Enzinger, who expanded the observations in a larger series in 1985. He defined a sarcoma with a peak incidence in young adult males and a predilection for extremities, involving subcutis or deeper tissue and extending along tendon sheaths or aponeuroses. The tumor forms nodules with central necrosis surrounded by bland polygonal cells with eosinophilic cytoplasm and peripheral spindling. Fibromalike, angiomatoid, and proximal aggressive variants (with larger cells, prominent nuceloi, and rhabdoid change) have since been described. Epithelioid sarcomas regularly express vimentin, cytokeratins, and epithelial membrane antigen, and about half are positive for CD34, but a wide range of other antigens can be expressed. S100 protein, desmin, and FLI-1 are usually negative. The ultrastructure displays epithelial and mesenchymal features including myofibroblastic differentiation. There are no specific genetic findings but several cases display chromosomal abnormalities in the 22q region. The tumor has no normal cellular counterpart and differs from both synovial sarcoma and carcinoma. There is a wide differential diagnosis from numerous benign and malignant conditions, including granuloma annulare, melanoma, and epithelioid vascular neoplasms. Epithelioid sarcoma has a high recurrence rate, which can be reduced by adequate surgery, and up to 40% metastasize, to regional lymph nodes, to lung, and other locations including scalp. Adverse prognostic factors include large size, male sex, older age, necrosis, vascular invasion, rhabdoid cytomorphology, and inadequate excision. Thirty-six years after Enzinger's original account, epithelioid sarcoma remains a clinically and pathologically distinct, indolent but aggressive sarcoma of indeterminate lineage.

[Historical development of grading of malignant soft tissue tumors]. / Historische Entwicklung der Graduierung von malignen Weichgewebstumoren.

This article describes the historical development of the grading systems for malignant soft tissue tumors. First attempts to grade these tumors were made in the middle of the nineteenth century; a remarkable amount of activity in grading took place in the 1970s with an apex in the 1980s. Reviewing the literature back to the first available publications, five phases in the development of the grading systems for malignant soft tissue tumors could be distinguished: 1845-1919: phase of identification, 1927-1964: phase of description, 1965-1977: phase of predominant mitotic activity, 1979-1983: phase of predominant tumor type, from 1984: phase of multifactorial systems.

Diagnostic gold standard for soft tissue tumours: morphology or molecular genetics?

The recognition of recurrent genetic alterations in specific tumour types has provided the basis for the reclassification of certain soft tissue neoplasms, and molecular analysis of patient material has the potential to provide both diagnostic and prognostic information. In this review, we evaluate the role of molecular genetic testing as the prospective 'gold standard' for sarcoma diagnosis. Molecular genetic testing, as with every new method, promises to improve accuracy and to be more sensitive and less subjective, claims that have been made previously by histochemistry, electron microscopy and immunohistochemistry. Technical limitations in molecular assays, as well as more general specificity issues, decrease the clinical usefulness of molecular pathological testing significantly and suggest that, at present, molecular evaluation is best considered an ancillary technique that neither supersedes other ancillary techniques nor eclipses traditional pathological examination.