Pseudomyogenic Haemangioendothelioma Research Articles

Perineal mass in a 50-year-old man

A man in his fifties presented with a lump in his left anal/perineal region, which was clinically thought to be a lipoma and was excised. No preoperative imaging was available....

Advances in the clinicopathological and molecular classification of cutaneous mesenchymal neoplasms.

In recent years, there have been several important refinements in the classification of cutaneous mesenchymal neoplasms, including the description of new tumour types, along with the identification of novel and recurrent molecular genetic findings. In addition to providing new insights into tumour biology, many of these advances have had significant clinical consequences with regard to diagnostics, management, and prognostication. Newly described entities include pseudomyogenic haemangioendothelioma, haemosiderotic fibrolipomatous tumour, and fibroblastic connective tissue naevus, which are reviewed in the context of the principal differential diagnoses and significant clinical implications. Genetic characterization of several soft tissue tumour types that occur in the skin has resulted in the identification of diagnostically useful markers: ALK gene rearrangement with corresponding ALK protein expression by immunohistochemistry in epithelioid fibrous histiocytoma; the WWTR1-CAMTA1 fusion gene with CAMTA1 protein expression in epithelioid haemangioendothelioma; MYC amplification and overexpression in radiation-associated angiosarcoma; and EWSR1 gene rearrangement in cutaneous myoepithelial tumours. Finally, the classification of intradermal smooth muscle tumours and unclassified/pleomorphic dermal sarcoma has been refined, resulting in both improved classification and improved prognostication. Many of the tumour types listed above are encountered not only by specialist dermatopathologists, but also by practising general surgical pathologists, and this review should therefore provide a widely applicable update on the histological and molecular classification of cutaneous mesenchymal neoplasms, along with the appropriate use of ancillary diagnostic tests, in particular immunohistochemistry, in the evaluation of such lesions and their histological mimics.

Challenging epithelioid mesenchymal neoplasms: mimics and traps

Epithelioid mesenchymal malignancies represent a major diagnostic challenge. Epithelioid morphology can be observed in a variety of soft tissue neoplasms, however there exist specific subtypes in which an epithelioid apperance constitutes the most distinctive morphological feature. Moving from epithelioid sarcoma of Enzinger (the prototype of sarcoma with epithelioid morphology), this review will focus on the most relevant entities: namely epithelioid haemangioendothelioma and angiosarcoma, pseudomyogenic haemangioendothelioma, epithelioid malignant peripheral nerve sheath tumour, epithelioid sclerosing fibrosarcoma, epithelioid pleomorphic liposarcoma, alveolar soft part sarcoma, and undifferentiated soft tissue sarcoma with epithelioid morphology. Differential diagnoses and major pitfalls will be discussed in detail.

WHO classification of soft tissue tumours: an update based on the 2013 (4th) edition

The fourth edition of the World Health Organization (WHO) Classification of Tumours of Soft Tissue and Bone was published in February 2013, and serves to provide an updated classification scheme and reproducible diagnostic criteria for pathologists. Given the relative rarity of soft tissue tumours and the rapid rate of immunohistochemical and genetic/molecular developments (not infrequently facilitating recognition of new tumour entities), this updated text edited by a consensus group is important for both practising pathologists and oncologists. The 2013 WHO classification includes several changes in soft tissue tumour classification, including several new entities (e.g., pseudomyogenic haemangioendothelioma, haemosiderotic fibrolipomatous tumour, and acral fibromyxoma), three newly included sections for gastrointestinal stromal tumours, nerve sheath tumours, and undifferentiated/unclassified soft tissue tumours, respectively, various 'reclassified' tumours, and a plethora of new genetic and molecular data for established tumour types that facilitate better definition and are useful as diagnostic tools. This article briefly outlines these updates based on the 2013 WHO classification of soft tissue tumours.

A novel SERPINE1–FOSB fusion gene results in transcriptional up‐regulation of FOSB in pseudomyogenic haemangioendothelioma

Pseudomyogenic haemangioendothelioma (PHE) is an intermediate malignant vascular soft tissue tumour primarily affecting children and young adults. The molecular basis of this neoplasm is unknown. We here used chromosome banding analysis, fluorescence in situ hybridization (FISH), mRNA sequencing, RT-PCR and quantitative real-time PCR on a series of morphologically well-characterized PHEs to show that a balanced translocation, t(7;19)(q22;q13), detected as the sole cytogenetic aberration in two cases, results in fusion of the SERPINE1 and FOSB genes. This translocation has not been observed in any other bone or soft tissue tumour. Interphase FISH on sections from eight additional PHEs identified the same SERPINE1-FOSB fusion in all cases. The role of SERPINE1, which is highly expressed in vascular cells, in this gene fusion is probably to provide a strong promoter for FOSB, which was found to be expressed at higher levels in PHEs than in other soft tissue tumours. FOSB encodes a transcription factor belonging to the FOS family of proteins, which, together with members of the JUN family of transcription factors, are major components of the activating protein 1 (AP-1) complex. Further studies are needed to understand the cellular impact of the aberrant expression of the FOSB gene, but as the t(7;19) resulting in the SERPINE1-FOSB fusion seems to be pathognomonic for PHE, FISH or RT-PCR could be useful for differential diagnostic purposes.

Men in red

Cutaneous vascular tumours are plentiful and represent one of the most common groups of soft tissue proliferations presenting in the skin. In the majority of cases the histological diagnosis of a cutaneous vascular is straightforward and most lesions are benign. Pathologists face three very challenging tasks when confronted with a skin biopsy containing a vascular proliferation. The first pertains to benign vascular lesions that are often confused with malignancy. This group of lesions includes lesions such as symplastic haemangioma, cutaneous angiomatous nodule, benign lymphangioendothelioma and the atypical vascular lesion arising after radiotherapy amongst others. The second relates to the recognition and accurate diagnosis of low-grade malignant vascular tumours. These tumours are rare and difficult to diagnose and some have been identified recently including pseudomyogenic haemangioendothelioma. The third refers to the accurate diagnosis of poorly differentiated malignant vascular tumours. This task is usually greatly aided by the judicious use of immunohistochemistry including fairly specific vascular markers such as CD31 and the more recently described FLI-1 and particularly ERG. ERG gene fusions occur in subsets of prostatic carcinoma, acute myeloid leukaemia and Ewing sarcoma. ERG is a highly specific marker of endothelial cell differentiation.

Rarely metastasizing soft tissue tumours

Soft tissue tumours that rarely metastasize have been afforded their own subcategory in recent WHO classifications. This review discusses the nature of these tumours and the difficulty in constructing usefully simple classifications for heterogeneous and complex groups of tumours. We also highlight the specific rarely metastasizing soft tissue tumours that have been recently added to the WHO classification (phosphaturic mesenchymal tumour, pseudomyogenic haemangioendothelioma) and those entities where there have been recent important defining genetic discoveries (myxoinflammatory fibroblastic sarcoma, solitary fibrous tumour, myoepitheliomas).

Primary pseudomyogenic haemangioendothelioma of bone

Pseudomyogenic haemangioendothelioma is a recently described vascular neoplasm that occurs most commonly in the soft tissue of distal extremities of young adults. Occurrence outside the somatic soft tissue has not been described thus far. We present here a unique case of pseudomyogenic haemangioendothelioma that arose in the long tubular bones of the lower extremity. The initial open biopsy was interpreted as a fibrous histiocytoma. However, the curettage specimen showed prominent epithelioid cytomorphology with a striking rhabdomyoblast-like appearance. By immunohistochemistry, the linear membranous staining of CD31 was highly suggestive of endothelial differentiation of the tumour cells. To the best of our knowledge, this case represents the first example of primary pseudomyogenic haemangioendothelioma of bone. Clinical and pathological correlation with application of immunohistochemistry is mandatory in establishing the correct diagnosis and excluding tumours with overlapping features.