Cutaneous Mesenchymal Neoplasms Research Articles

TRPS1 Expression Is Frequently Seen in a Subset of Cutaneous Mesenchymal Neoplasms and Tumors of Uncertain Differentiation: A Potential Diagnostic Pitfall.

Although extensively studied in cutaneous epithelial neoplasms, the TRPS1 immunoreactivity in cutaneous mesenchymal neoplasms and tumors of uncertain differentiation (CMNTUDs), such as atypical fibroxanthoma (AFX), remains largely unexplored. We assessed TRPS1 immunoreactivity in 135 CMNTUDs, comprising 46 fibrohistiocytic/fibroblastic tumors, 28 vascular tumors, 24 peripheral nerve sheath tumors (PNSTs), 21 tumors of uncertain differentiation, and 16 smooth muscle tumors. Additionally, we included selected cases of melanoma with spindled cell morphology or desmoplastic features (n = 9) and sarcomatoid squamous cell carcinoma (SSCC) (n = 5) to compare TRPS1 expression patterns with those of AFX. TRPS1 expression was prevalent in dermatofibromas (24/24), leiomyomas (8/8), AFXs/pleomorphic dermal sarcoma (PDS) (20/21), dermatofibrosarcomas protuberans (14/22), and leiomyosarcomas (6/8). It was uncommon in angiosarcomas (3/20), Kaposi sarcomas (2/8), and neurofibromas (5/17) and absent in perineuriomas (0/2). AFXs/PDS exhibited the highest median H-score of 240, contrasting with minimal TRPS1 immunoreactivity in vascular neoplasms and PNSTs, with median H-scores consistently below 10. Significant differences in H-score were observed between AFXs/PDS and angiosarcomas (p < 0.001), melanomas (p < 0.001), and leiomyosarcomas (p = 0.029). However, no significant difference was found compared to SSCCs, suggesting limited discriminatory power of TRPS1 in this context. This study sheds light on TRPS1 expression patterns in a subset of CMNTUDs, extending beyond prior studies primarily focused on epithelial tumors, while underscoring potential pitfalls associated with TRPS1 immunohistochemistry.

Gene fusions in superficial mesenchymal neoplasms: Emerging entities and useful diagnostic adjuncts.

Cutaneous mesenchymal neoplasms are diagnostically challenging because of their overlapping morphology, and, often, the limited tissue in skin biopsy specimens. Molecular and cytogenetic techniques have identified characteristic gene fusions in many of these tumor types, findings that have expanded our understanding of disease pathogenesis and motivated development of useful ancillary diagnostic tools. Here, we provide an update of new findings in tumor types that can occur in the skin and superficial subcutis, including dermatofibrosarcoma protuberans, benign fibrous histiocytoma, epithelioid fibrous histiocytoma, angiomatoid fibrous histiocytoma, glomus tumor, myopericytoma/myofibroma, non-neural granular cell tumor, CIC-rearranged sarcoma, hybrid schwannoma/perineurioma, and clear cell sarcoma. We also discuss recently described and emerging tumor types that can occur in superficial locations and that harbor gene fusions, including nested glomoid neoplasm with GLI1 alterations, clear cell tumor with melanocytic differentiation and ACTIN::MITF translocation, melanocytic tumor with CRTC1::TRIM11 fusion, EWSR1::SMAD3-rearranged fibroblastic tumor, PLAG1-rearranged fibroblastic tumor, and superficial ALK-rearranged myxoid spindle cell neoplasm. When possible, we discuss how fusion events mediate the pathogenesis of these tumor types, and we also discuss the related diagnostic and therapeutic implications of these events.

Fine needle aspiration cytopathology of pleomorphic dermal sarcoma.

Pleomorphic dermal sarcoma (PDS) is an uncommon cutaneous mesenchymal neoplasm. It is cytomorphologically identical to atypical fibroxanthoma (AFX), but differs due to its invasion beyond the dermis. We undertook an examination of our experience with fine needle aspiration (FNA) biopsy cytology of PDS. Our cytopathology files were searched for examples of PDS with concomitant histopathological verification. FNA biopsy smears and cell collection were performed using standard techniques. Seven cases of PDS were retrieved from four different patients (M:F, 1:1; age range: 63-88 years; mean age = 78 years). All patients (57%) presented with a primary tumour with one having an FNA biopsy of two local recurrences and a single distant metastasis. Five aspirates were from the extremities and two from the head/neck. Tumours ranged from 1.0 to 3.5 cm (mean, 2.2 cm). Specific cytological diagnoses were pleomorphic spindle/epithelioid sarcoma (3 cases), PDS (2), AFX (1), and atypical myofibroblastic lesion, query nodular fasciitis (1). Immunohistochemical (IHC) staining from FNA-generated cell blocks in two cases showed non-specific staining with vimentin in both cases; positive CD10, CD68, and INI-1 staining in one case; and smooth muscle actin expression in the other. Multiple negative stains were performed in both of these cases to exclude malignant melanoma, carcinoma, and specific forms of sarcoma. Cytopathology consisted of a mixture of spindle, epithelioid, and bizarre pleomorphic cells. Coupled with ancillary IHC stains, FNA biopsy can help recognise PDS as a sarcomatous cutaneous neoplasm, but is unable to distinguish PDS from AFX.

Diagnostic utility of ERG immunostaining in dermatofibroma

AimsDermatofibroma/fibrous histiocytoma (DF/FH) is a common cutaneous mesenchymal neoplasm exhibiting benign biological behaviour. However, the immunohistochemical utility of erythroblast transformation-specific-related gene (ERG) for diagnosing DF remains unknown. The authors reviewed...

Recent advances in the diagnosis, classification and molecular pathogenesis of cutaneous mesenchymal neoplasms.

The diagnosis of cutaneous mesenchymal neoplasms remains challenging, due to a combination of overlapping histological features, the rarity of some diagnoses and often inadequate sampling in superficial biopsies. Here, we describe recent advances in cutaneous mesenchymal neoplasms. We discuss improvements in our understanding of the molecular pathogenesis of non-neural granular cell tumour, epithelioid fibrous histiocytoma, composite and retiform haemangioendothelioma and dermatofibrosarcoma protuberans. We also discuss recently described tumour types, including some discovered via molecular testing: EWSR1::SMAD3-rearranged fibroblastic tumour, clear cell neoplasm with MITF::CREM rearrangement and melanocytoma with CRCT1::TRIM11 rearrangement, and some discovered via traditional histopathology: superficial CD34-positive fibroblastic tumour, plexiform myofibroblastoma and clear cell neoplasm with melanocytic differentiation and ACTIN::MITF translocation.

Epithelioid Cutaneous Mesenchymal Neoplasms: A Practical Diagnostic Approach.

Epithelioid cells are rounded or polygonal cells with abundant eosinophilic or clear cytoplasm and ovoid to round nuclei, superficially resembling epithelial cells. Cutaneous mesenchymal neoplasms composed predominantly or exclusively of epithelioid cells are relatively uncommon and can cause considerable diagnostic difficulties due to overlapping histologic features among heterogeneous groups of tumors. Familiarity with practical diagnostic approaches and recognition of key histopathologic features are important for correct diagnosis and management. This review summarizes the histologic features of epithelioid cutaneous mesenchymal neoplasms and discusses their differential diagnoses from malignant melanomas and carcinomas.

Cutaneous soft tissue tumors: how do we make sense of fibrous and "fibrohistiocytic" tumors with confusing names and similar appearances?

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.

Multiple Fixed Drug Eruption Due to Piroxicam: A Brief Case Report

Atypical Fibroxanthoma (AFX) is a rare cutaneous mesenchymal neoplasm, predominantly found on sun-damaged skin of the head and neck in elderly patients. But uncommonly it can develop on a burn scar with or without actinic damage. Malignancy development is the major complication of severe burns and the term Marjolin's ulcer has been accepted clinically. The most common malignancy in this setting are Squamous Cell Carcinoma (SCC), followed by Basal Cell Carcinoma (BCC) and Malignant Melanoma (MM). Mesenchymal tumours especially malign forms quite infrequently seen on scar tissue. Herein, we present a rare and unusual case of AFX arising on the non sun-damaged area within a chronic burn scar of a young patient. Four cases of burn-related AFX reported in the literature are reviewed and the histopathological features and differential diagnosis are discussed.

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.

Glomangiosarcoma de novo in a child: A case report and review of literature

Glomus tumors (GT) are cutaneous and soft tissue mesenchymal neoplasms. The malignant variant that is, glomangiosarcomas (GS) are rare and account for <1% of all GT. GS are usually seen in adults with a wide age range of 20-89 years. GS usually have an indolent course with local aggressiveness. The treatment is complete surgical excision with excellent prognosis though metastasis workup is advised. Herein, we report an unusually large GS de novo in a 6-year-old girl. Complete surgical excision was performed. There was no evidence of recurrence or metastasis over the last 15 months of follow-up postoperatively. GS should be considered as one of the differential diagnosis of cutaneous and soft tissue neoplasms.

Cellular Neurothekeoma With Fascicular Growth Features Mimicking Cellular Dermatofibroma

Cellular neurothekeoma (CNT) is a benign cutaneous mesenchymal neoplasm. Most demonstrate a lobulated to micronodular architecture. Rarely, CNT demonstrates a predominantly fascicular growth pattern, without prominent sclerosis and thus can mimic cellular dermatofibroma (DF). Three CNT with a predominantly fascicular pattern were obtained. The clinicopathologic features and accompanying immunohistochemical stains were evaluated. All cases demonstrated a moderately cellular proliferation of epithelioid to spindle cells with pale to eosinophilic slightly granular cytoplasm, vesicular nuclei, and a single nucleolus arranged in a fascicular pattern with thick collagen bundles at the periphery (collagen trapping). One case had prominent epidermal hyperplasia. The neoplastic cells expressed NKI-C3, CD10, and micropthalmia transcription factor and lacked expression of factor XIIIa, S-100, epithelial membrane antigen, and CD34. Our cases showed an unusual pattern of CNT with a predominantly fascicular growth pattern, thickened collagen bundles at the periphery, and occasionally epidermal hyperplasia. The overlap with cellular DF is striking. The presence of plump to epithelioid cytomorphology with abundant cytoplasm, with focally prominent nucleoli; the presence of focal lobulated to micronodular growth pattern along with micropthalmia transcription factor positivity; and lack of factor XIIIa expression are helpful in distinguishing fascicular CNT from cellular DFs.

Development of Dermatomyofibroma in a Male Infant

Dermatomyofibroma is a rare benign cutaneous mesenchymal neoplasm of the fibroblasts and myofibroblasts. The majority of dermatomyofibromas present as red-brown discolored plaques or nodules, commonly located on the shoulder, upper arm, axilla, neck, and/or upper trunk. These lesions develop most frequently in young female patients at a mean of 28-years-of-age. Herein, a case of dermatomyofibroma is reported that developed in an infant. A 4-month-old boy presented with an ill-defined bluish firm plaque on the trunk that developed 1 month after birth. Histopathologically, there was proliferation of bland-looking spindle cells with fascicular arrangement in the dermis and subcutaneous tissue. Immunohistochemistry showed that most of the tumor cells expressed diffuse positivity for vimentin and smooth muscle actin, but were negative for S-100 protein, desmin, and CD34.

Two cases of dermatomyofibroma (plaque‐like dermal fibromatosis)

Dermatomyofibroma is a rare but distinct benign cutaneous mesenchymal neoplasm of fibroblastic/myofibroblastic differentiation. It is more common in adolescents and young adults, with a female preponderance. In most cases, the lesions are asymptomatic and small, measuring from 10 to 20 mm. Early and active lesions tend to be actin positive. We present a) a new case of dermatomyofibroma in an 11-month-old male infant, the youngest case reported to date, and b) the second reported case of a giant annular dermatomyofibroma, measuring 10 cm × 6 cm, in a 52-year-old woman. In both cases, histological examination showed a spindle-cell proliferation embedded among the collagen fibers of the dermis, arranged predominantly parallel to the skin surface. In both cases the spindle cells stained positive for smooth muscle actin and the elastic fibers were increased and fragmented. Dermatologists and pediatricians should be aware of this benign entity in order to avoid unnecessary treatment.

Dermatomyofibroma: Clinicopathologic and Immunohistochemical Analysis of 56 Cases and Reappraisal of a Rare and Distinct Cutaneous Neoplasm

Dermatomyofibroma represents a rare and distinct benign cutaneous mesenchymal neoplasm of fibroblastic/myofibroblastic differentiation. A series of 56 cases of dermatomyofibroma has been analyzed to further characterize the clinicopathologic spectrum of this entity. Forty patients were female and 8 were male (gender was unknown in 8 cases). Patients' age ranged from 3 to 51 years (mean 30.8 years, median 30 years). Interestingly, 6 patients were younger than 16 years, and in this age group, 3 male and 3 female patients, respectively, were noted. The shoulder (13 cases) was the anatomic site most commonly affected, followed by the upper arm (7 cases), the neck (6 cases), the thigh (6 cases), the chest wall (4 cases), the back (3 cases), the axillary fold (2 cases), the abdominal wall (2 cases), and 1 case each was seen on the forearm, the buttock, and the popliteal fossa (exact anatomic location was unknown in 10 cases). One patient presented with 2 lesions arising simultaneously on both shoulders. Histologically, an ill-defined, plaque-like dermal neoplasm of varying cellularity was seen in all cases, composed of bland spindle-shaped tumor cells often oriented parallel to the overlying epidermis. An infiltration of superficial part of the subcutis was seen in 23 cases, and in 6 cases, deeper parts of the subcutis were involved by often perpendicular growing bands of neoplastic cells. Immunohistochemically, tumor cells in 11 of 48 cases tested stained positively for alpha-smooth muscle actin, and a focal expression of this marker was noted in 20 cases. In addition, a focal expression of CD34 was seen in 10 of 45 cases tested. Follow-up information was available in 38 cases (range from 3 to 156 months, median 34 months), and despite marginal or incomplete excision in 17 cases, none of the cases recurred. Dermatomyofibroma represents a benign fibroblastic/myofibroblastic dermal neoplasm.

Haemorrhagic dermatomyofibroma (plaque-like dermal fibromatosis): clinicopathological and immunohistochemical analysis of three cases resembling plaque-stage Kaposi's sarcoma.

Dermatomyofibroma (plaque-like dermal fibromatosis) represents a distinct clinicopathological entity in the spectrum of cutaneous mesenchymal neoplasms showing a myofibroblastic line of differentiation. These benign neoplasms occur frequently, but not exclusively, in young women, and the shoulder girdle as well as the upper trunk are common locations. Histologically, dermatomyofibroma is characterized by a plaque-like proliferation of cytologically bland spindle-shaped tumour cells containing an ill-defined, pale eosinophilic cytoplasm and elongated, neuroid nuclei. Neoplastic cells are arranged in bundles and fascicles orientated parallel to the skin surface, adnexal structures are spared and elastic fibres are increased and fragmented. Immunohistochemically, tumour cells express vimentin and variably muscle actin and alpha-smooth muscle actin, but are negative for desmin, CD34, S100, and epithelial markers. The main differential diagnosis includes hypertrophic scar, dermatofibroma (fibrous histiocytoma), pilar leiomyoma, neurofibroma, adult myofibromatosis, extra-abdominal fibromatosis and plaque-stage dermatofibrosarcoma protuberans. We report three cases of dermatofibroma arising in male patients aged 31, 36, and 47 years on the thigh, chest wall and back, respectively. All lesions were completely excised and no local recurrence has been reported. Histologically, the neoplasms showed classical features of dermatomyofibroma; however, in addition abundant extravasated erythrocytes, scattered inflammatory cells, numerous capillaries, and sieve- and slit-like spaces, features resembling plaque-stage Kaposi's sarcoma, were noted. In none of the cases did spindled tumour cells stain positively for CD34, and HHV8 was not detected by polymerase chain reaction. The reported cases widen the clinicopathological spectrum of dermatomyofibroma and emphasize plaque-stage Kaposi's sarcoma as an additional differential diagnosis.

Caveolin Expression is Common among Benign and Malignant Smooth Muscle and Adipocyte Neoplasms

The caveolins belong to a newly described group of membrane-scaffolding proteins. Their presence in benign endothelial cells has been used to discriminate benign from malignant vascular neoplasms. The extent of caveolin expression in cutaneous mesenchymal neoplasms has not yet been evaluated, and thus the diagnostic utility of these antibodies is not yet known. In our study, we immunohistochemically examined a spectrum of tumors derived from smooth muscle and adipocytes for caveolin expression. We found that both benign and malignant smooth muscle tumors and tumors comprised of adipocytes expressed caveolins. The presence of this protein in a range of mesenchymal neoplasms is important to know about as this decreases the reported specificity of a positive finding. It is doubtful that caveolin down-regulation contributes to the pathogenesis of liposarcomas and leiomyosarcomas. This finding also may suggest a common origin between endothelial cells and other mesenchymal cells.