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In the 2018 World Health Organization Classification of Skin Tumors, a wide range of predominantly benign mesenchymal neoplasms are included in the fibroblastic, myofibroblastic, and "fibrohistiocytic" categories. By far the most common of these tumors is dermatofibroma (fibrous histiocytoma). There are many histologic variants of dermatofibroma, some of which (cellular, aneurysmal, and atypical) are associated with a higher risk of local recurrence; these variants may be mistaken for more aggressive tumor types, including sarcomas. Furthermore, distinguishing among the fibrous and "fibrohistiocytic" tumors can be a diagnostic challenge, given their sometimes-similar histologic appearances and confusing nomenclature. Immunohistochemistry and molecular genetic assays play a relatively limited role in the diagnosis of these tumor types, with notable exceptions (i.e., epithelioid fibrous histiocytoma and dermatofibrosarcoma protuberans). Proper recognition of dermatofibrosarcoma protuberans is critical, since this tumor type is associated with locally aggressive behavior; transformation to the fibrosarcomatous variant brings metastatic potential. In recent years, understanding of the molecular pathogenetic basis for cutaneous mesenchymal neoplasms has increased dramatically, with the discovery of gene rearrangements in some of these tumor types. In this review, the histologic features of the most common fibrous and "fibrohistiocytic" cutaneous mesenchymal neoplasms will be discussed, as well as recently identified molecular genetic alterations.

Cutaneous soft tissue tumors with epithelioid features present a diagnostic challenge given that many entities in this category are rare, and they show morphologic overlap with significantly more common cutaneous epithelial and melanocytic neoplasms. The challenge is compounded by overlapping expression of epithelial or melanocytic markers in some of these entities. A broad spectrum of primary cutaneous epithelioid soft tissue tumors exists, including benign and malignant counterparts of tumors with various differentiation including melanocytic, peripheral nerve sheath, angiomatous, fibrohistiocytic, and myoid or myoepithelial, in addition to translocation-associated tumors lacking a derivative tissue type. Given this spectrum, an initial targeted immunohistochemical panel for epithelioid dermal and subcutaneous neoplasms is recommended, covering a broad spectrum of differentiation. In diagnostically challenging cases, select molecular studies can be employed to make critical distinctions between entities sharing morphologic and immunohistochemical properties. Due to sometimes marked differences in prognosis and treatment, knowledge and familiarity with epithelioid soft tissue tumors is key for any surgical pathologist who evaluates skin and subcutaneous biopsies and excision specimens. This concise review provides brief descriptions, key diagnostic features, and important modern ancillary studies for the diagnosis of non-epithelial, non-melanocytic cutaneous tumors that can exhibit a prominent degree of epithelioid morphology.

Cutaneous mesenchymal neoplasms often pose significant diagnostic challenges; many such entities are rare or show clinical and histologic overlap with both other mesenchymal and non-mesenchymal lesions. Recent advances in the genetic classification of many cutaneous mesenchymal neoplasms have not only helped define unique pathologic entities and increase our understanding of their biology, but have also provided new diagnostic markers. This review details these recent discoveries, with a focus on their implications for tumor classification and diagnosis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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., (© 2016 John Wiley & Sons Ltd.)

So-called fibrohistiocytic tumors of the skin comprise a heterogeneous spectrum of superficially located neoplasms that often show fibroblastic and/or myofibroblastic differentiation. In this review clinicopathologically important variants of dermatofibroma and dermatofibrosarcoma protuberans and their differential diagnoses are discussed in detail. In addition, the clinicopathological features of atypical fibroxanthoma, angiomatoid fibrous histiocytoma, plexiform fibrohistiocytic tumors and pleomorphic dermal sarcoma are presented. Entities that have to be considered in the differential diagnosis are also mentioned.

Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare tumors mainly occurring in early childhood. Our recent results showed that ectopic overexpression of human Prox1 gene, a lymphatic endothelial nuclear transcription factor, promoted an aggressive behavior in 2 murine models of KHE. This dramatic Prox1-induced phenotype prompted us to investigate immunohistochemical staining pattern of Prox1, podoplanin (D2-40), LYVE-1, and Prox1/CD34 as well as double immunofluorescent staining pattern of LYVE-1/CD31 in KHE and TA, compared with other pediatric vascular tumors. For this purpose, we examined 75 vascular lesions: KHE (n=18), TA (n=13), infantile hemangioma (n=13), pyogenic granuloma (n=18), and granulation tissue (n=13). Overall, KHE and TA shared an identical endothelial immunophenotype: the neoplastic spindle cells were Prox1, podoplanin, LYVE-1, CD31, and CD34, whereas endothelial cells within glomeruloid foci were Prox1, podoplanin, LYVE-1, CD31, and CD34. The lesional cells of all infantile hemangiomas and pyogenic granulomas were negative for Prox1 in the presence of positive internal control. These findings provide immunophenotypic evidence to support a preexisting notion that KHE and TA are closely related, if not identical. Overall, our results show, for the first time, that Prox1 is an immunohistochemical biomarker helpful in confirming the diagnosis of KHE/TA and in distinguishing it from infantile hemangioma and pyogenic granuloma.

Context: Dermatopathology covers a large variety of entities, some having very similar histologic appearances. Immunohistochemistry is an incredibly helpful tool that is useful in diagnosis as well as prognosis of selected skin tumors., Objective: To provide a comprehensive review of recent trends and immunohistochemical stains used by dermatopathologists. Emphasis is placed on new stains as well as novel uses of existing stains., Data Sources: All data were gathered from published journal articles available through the National Center for Biotechnology Information PubMed database., Conclusions: New immunohistochemical targets are continually being found, contributing to more accurate diagnosis and classification of skin tumors. The presence of specific markers can be used to determine the aggressiveness of malignancies and design treatment strategies. In addition, application of existing stains can help determine intravascular spread of malignancy in primary cutaneous lesions. And use of rapid immunohistochemical staining techniques on frozen sections can assist in more complete excision of tumor margins. Immunohistochemistry is a highly versatile and growing tool of dermatopathologists.

Infantile cutaneous hemangioma is a benign vascular tumour present at 10% of the infants. It forms part of the group of the vascular tumours in the classification of International Society for Vascular Anomalies (ISSVA). Clinical diagnosis is easy in its triphasic typical form with a phase of sometimes brutal postnatal growth, a phase of stabilization and a phase of slow secondary regression. Classically, it is presented in the form of a mass or stains cutaneous red, of a subcutaneous mass or, generally, of a mixed form associating the two aspects.

Mesenchymal tumors are a heterogeneous group of tumors often arising in the skin and soft tissue. The tumors have been reclassified by the WHO in 2002. Benign mesenchymal tumors are about a hundred times more frequent than malignant mesenchymal tumors. Clinically, mesenchymal tumors often present as skin-colored nodes. Overall, elderly persons are more affected than younger individuals. The etiology is often unknown, sometimes there is an association with insults such as radiation, scars, or lymphedematous or venous stasis. Whereas some years ago a wide excision with a margin of 3-5 cm was performed for malignant variants, today micrographic surgery is preferred, as it can avoid mutilating procedures. Early detection and removal is critical since mesenchymal skin tumors often cannot be cured by radiation or chemotherapy.

Atypical fatty tumors present problems of terminology and diagnosis. While atypical fatty tumors that are located in subcutaneous tissues have an extremely good prognosis, local recurrence and transformation to a higher grade tumor may occur. Allen et al document the morphologic features and behavior of 37 atypical subcutaneous fatty tumors and describe a system of grading. The commentary discusses the terminology of atypical fatty tumors, the relevance of the proposed grading system, and the significance of a spindle cell component in atypical subcutaneous fatty tumors.

Dermatofibrosarcoma protuberans (DFSP), atypical fibroxanthoma (AFX), and malignant fibrous histiocytoma (MFH) are rare soft tissue sarcomas of intermediate to high-grade malignancy that the dermatologist must evaluate and treat. DFSP is a fibrohistiocytic tumor of intermediate malignancy characterized by aggressive local growth and propensity to recur after surgical excision. AFX is a superficial malignant tumor that arises on sun-exposed surfaces and is characterized by local aggressive behavior. MFH is the most aggressive of the fibrohistiocytic tumors with a high local recurrence rate and significant metastatic rate usually associated with a poor prognosis. This article reviews the epidemiology, pathogenesis, clinical presentation, histology, management, prognosis, and follow-up of these malignant tumors.

Superficial, especially cutaneous soft tissue tumors deserve attention because of their special biology, often with better prognosis than their deep counterparts. This fact also has been considered in the TNM Classification/UICC, as well as in the Typing of Soft Tissue Tumors/WHO.-Basically all types of soft tissue tumors can also be found in subcutaneous and cutaneous localisation. Dermatofibrosarcoma protuberans, however, is a typical superficial tumor involving cutis and frequently the superficial subcutis. Superficial leiomyosarcoma and atypical fibroxanthoma are examples of sarcomas, which in spite of histological criteria, which generally are associated with high grade malignancy, behave as low grade malignant tumors, i.e. chiefly with risk of recurrency albeit negligible risk of metastases. Angiosarcoma and epitheloid sarcoma, on the other hand, may also metastasize, even if restricted to the cutis. Here histological criteria as numerous mitoses, cellular atypia and tumor necrosis, may additionally influence the prognosis. In conclusion it is evident that exact tumor classification is the basic requirement for an optimal, prognosis-adapted therapy. Prerequisite, however, is a precise clinico-pathological correlation to understand the biology of the different tumor entities.

Connective tissue tumours represent a significant group among biopsied skin lesions and manifest a wide range of morphological patterns. While the majority are easily diagnosed, notably most fibrous histiocytomas and neural lesions, a proportion pose considerable diagnostic difficulty. With the increasing recognition and characterisation of previously undescribed entities within the family of soft tissue tumours in recent years, the number of unclassifiable lesions should diminish. The ultimate aim of accurate recognition and classification is to provide appropriate clinical care based on reasoned prediction of a given lesion's behaviour. With this in mind, we wish to briefly review herein some of the more recently characterised dermal connective tissue lesions, including plexiform fibrohistiocytic tumour, cellular fibrous histiocytoma, spindle celled atypical fibroxanthoma, adult myofibroma, dermatomyofibroma, so-called cellular neurothekeoma, ectopic meningothelial hamartoma, tufted angioma, sinusoidal haemangioma and bacillary angiomatosis.