Histopathologic Evaluation of Atypical Fibroxanthoma or Pleomorphic Dermal Sarcoma Debulk Specimen from Mohs Surgery: A Requirement for Their Proper Distinction.

Pleomorphic dermal sarcomas can be clinically aggressive, with a higher tendency to cause local recurrence, metastasis, and death. Atypical fibroxanthoma and pleomorphic dermal sarcoma are histopathologically similar, and their distinction requires a systematic examination of the entire excised tumor. Since Mohs micrographic surgery is commonly utilized to treat atypical fibroxanthoma, a histopathologic evaluation of debulk specimens by permanent pathology is prudent to avoid underdiagnosing pleomorphic dermal sarcoma. This approach can improve risk assessment and treatment decisions, ultimately enhancing patient outcomes. Also, the proper distinction will facilitate the future development of accurate staging criteria and additional treatment modalities.

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.

Retrospective Single-Center Case Study of Clinical Variables and the Degree of Actinic Elastosis Associated with Rare Skin Cancers.

(1) Background: Rare skin cancers include epithelial, neuroendocrine, and hematopoietic neoplasias as well as cutaneous sarcomas. Ultraviolet (UV) radiation and sunburns are important drivers for the incidence of certain cutaneous sarcomas; however, the pathogenetic role of UV light is less clear in rare skin cancers compared to keratinocyte cancer and melanoma. In this study, we compared the degree of actinic elastosis (AE) as a surrogate for lifetime UV exposure among selected rare skin cancers (atypical fibroxanthoma [AFX], pleomorphic dermal sarcoma [PDS], dermatofibrosarcoma protuberans [DFSP], Kaposi sarcoma [KS], Merkel cell carcinoma [MCC], and leiomyosarcoma [LMS]) while taking into account relevant clinical variables (age, sex, and body site). (2) Methods: We newly established a semi-quantitative score for the degree of AE ranging from 0 = none to 3 = total loss of elastic fibers (basophilic degeneration) and multiplied it by the perilesional vertical extent (depth), measured histometrically (tumor-associated elastosis grade (TEG)). We matched the TEG of n = 210 rare skin cancers from 210 patients with their clinical variables. (3) Results: TEG values were correlated with age and whether tumors arose on UV-exposed body sites. TEG values were significantly higher in AFX and PDS cases compared to all other analyzed rare skin cancer types. As expected, TEG values were low in DFSP and KS, while MCC cases exhibited intermediate TEG values. (4) Conclusions: High cumulative UV exposure is more strongly associated with AFX/PDS and MCC than with other rare skin cancers. These important results expand the available data associated with rare skin cancers while also offering insight into the value of differentiating among these tumor types based on their relationship with sun exposure, potentially informing preventative, diagnostic and/or therapeutic approaches.

Orbital invasion of a conjunctival atypical fibroxanthoma in a patient with systemic diffuse large B-cell lymphoma.

An 88-year-old male patient presented with a large mass on the left lateral bulbar conjunctiva. The tumor appeared two months after the resection of a conjunctival atypical fibroxanthoma (AFX) performed by a cornea specialist. Magnetic resonance imaging of the orbits showed deep orbital invasion along the lateral rectus muscle. The mass and the entire conjunctival sac were totally excised with lid-sparing orbital exenteration. Histopathological analysis confirmed that the mass was an extension of the AFX. Two weeks after surgery, large B-cell lymphoma was diagnosed in the oropharynx. Chemotherapy was initiated, and after seven months of follow-up, there was no recurrence of the AFX. The authors believe that this is the first report of orbital invasion by AFX.

Ex Vivo Confocal Laser Scanning Microscopy in Rare Skin Diseases.

While ex vivo confocal laser scanning microscopy has previously demonstrated its utility in most common skin diseases, its use in the assessment of dermatological entities with lower incidence remains unexplored in most cases. We therefore aimed to evaluate the diagnostic efficacy of some rare skin tumors as well as a few inflammatory skin diseases, that have not yet been studied in ex vivo confocal laser scanning microscopy. A total of 50 tissue samples comprising 10 healthy controls, 10 basal cell carcinoma, 10 squamous cell carcinoma, and 20 rare skin conditions were imaged using the newest generation ex vivo confocal microscopy (Vivascope 2500 M-G4, Vivascope GmbH, Munich, Germany). Three blinded investigators were asked to identify characteristic features of rare skin disorders and distinguish them from more common skin diseases in the ex vivo confocal microscopy images. Our findings present the capability of ex vivo confocal microscopy to display distinctive morphologic patterns in common and rare skin diseases. As might be expected, we found a strong correlation between imaging experience and diagnostic accuracy. While the imaging inexperienced dermatohistopathologist reached 60% concordance, the imaging-trained dermatologist obtained 88% agreement with dermatohistopathology. The imaging-trained dermatohistopathologist achieved concordance up to 92% with gold-standard dermatohistopathology. This study highlights the potential of ex vivo confocal laser scanning microscopy as a promising adjunct to conventional dermatohistopathology for the early and precise identification of rare dermatological disorders.

Case Study of Atypical Fibroxanthoma: Presentation and Management.

Atypical fibroxanthoma (AFX) is a rare spindle cell proliferation arising from significant sun exposure. AFX often appears as a red papule, typically found in the head and neck region of elderly patients. Since there is no specificity in immunohistology, various stains differentiate AFX from other skin cancers. The stains include cluster of differentiation 68 (CD68), cluster of differentiation 163 (CD163), vimentin, cytokeratin epithelial (CKAE), and melanin. While local recurrence is common, AFX rarely metastasizes. Thus, the treatment options are complete surgical excision or micrographically oriented histographic surgery.

Hydrochlorothiazide and increased risk of atypical fibroxanthoma and pleomorphic dermal sarcoma.

BACKGROUND AND OBJECTIVES: Previous work has demonstrated that hydrochlorothiazide (HCTZ) is a risk factor for squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) due to pro-photocarcinogenic effects. Atypical fibroxanthoma (AFX) and pleomorphic sarcoma (PDS), both ultraviolet-induced cancers, display a rare but rising cutaneous tumor entity. This study aimed to evaluate if the use of HCTZ is higher in patients with AFX/PDS than in patients with SCC/BCC and subsequently may be a risk factor for AFX/PDS-development. PATIENTS AND METHODS: In a retrospective study of four German skin cancer centers, AFX/PDS cases and SCC/BCC controls were sex and age matched (1:3) over a time-period of 7 years (2013-2019) to evaluate the use of HCTZ, immunosuppressive medication, second malignancies, and presence of diabetes mellitus. RESULTS: Overall, 146 AFX/PDS and 438 controls (SCC/BCC) were included in the study. The use of HCTZ was significantly higher in patients with AFX/PDS (44.5%) compared to patients with SCC/BCC (25.3%). Additionally, the presence of diabetes mellitus was significantly higher in AFX/PDS patients. CONCLUSIONS: This study demonstrates a significantly higher use of HCTZ in patients with AFX/PDS compared to SCC/BCC. This result suggests that HCTZ may be a risk factor for AFX/PDS. Additionally, diabetes mellitus or its comorbidities may be associated with an increased risk for AFX/PDS.

Atypical Fibroxanthoma Treated with a Topical Combination of Imiquimod, Tazarotene, and 5-Fluorouracil.

This case report describes an 80-year-old man who presented with a growing erythematous nodule with erosion, measuring 0.6 cm × 0.6 cm, on his right temple. This lesion was later diagnosed as atypical fibroxanthoma (AFX). Instead of undergoing Mohs surgery, the gold standard treatment, the patient opted to pursue a topical treatment regimen because of financial costs associated with surgical removal and repair. This topical regimen consisted of tazarotene cream, imiquimod cream, and 5-fluorouracil solution, applied for 30 days. The patient was directed to use this combination 5 days per week for 6 weeks. The specified dosage for each medication was a fifth of a packet of imiquimod 5% cream, an equivalent amount of tazarotene 0.1% cream, and a single drop of 5-fluorouracil 2% solution. These were combined on a bandage and placed on the lesion overnight. Following the treatment, a 3-week post-application examination revealed an erosion, 1.0 cm × 0.9 cm, amidst erythema. A subsequent incisional biopsy with histopathology and stains for CD10 and CD99, 3 weeks after treatment, and three punch biopsies with histopathology and stains for CD10 and CD99, 1-year post-treatment, confirmed the absence of AFX. AFX is a superficial variant of pleomorphic dermal sarcoma (PDS), which shares histologic similarities, yet the exact relationship between AFX/PDS and undifferentiated pleomorphic sarcoma is still not well understood. Previous studies have indicated a genomic similarity between AFX/PDS and cutaneous squamous cell carcinoma (cSCC), which suggests the potential efficacy of cSCC-targeted treatments for AFX/PDS. This case marks the first recorded instance of successful topical medical treatment of AFX, offering an alternative for patients who may opt out of surgical intervention. Continued research to assess the broader efficacy of this approach is encouraged.

Pleomorphic Dermal Sarcoma.

Pleomorphic dermal sarcoma (PDS) is a rare cutaneous/subcutaneous neoplasm of purported mesenchymal differentiation that exists along a clinicopathologic spectrum with atypical fibroxanthoma (AFX). While PDS and AFX share histopathologic and immunohistochemical features, PDS exhibits deeper tissue invasion and has a higher rate of metastasis and local recurrence than AFX. Given its aggressive clinical course, early recognition and clinical management of PDS are essential for optimizing patient outcomes. This review aims to provide a brief overview of the clinicopathologic and molecular features, prognosis, and treatment of PDS.

[Atypical fibroxanthoma]. / Atipicheskaya fibroksantoma.

Atypical fibroxanthoma (AFX) is a rare skin tumor characterized by a combination of a «malignant¼ morphological features and non-aggressive clinical course. Diagnosing AFX is challenging due to histological «diversity¼ and heterogeneous immunophenotype. The presented review describes the history and evolution of AFX as a nosological form of cancer, its histogenetic origin, pathogenesis and biological potential. The clinical, morphological, immunohistochemical, molecular cytogenetic characteristics and histological subtypes of the tumor as well as differential diagnosis have been presented in detail.

Atypical fibroxanthoma and pleomorphic dermal sarcoma: Local recurrence and metastasis in a nationwide population-based cohort of 1118 patients.

BACKGROUND: The prognosis of patients with atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) remains uncertain and no standardized follow-up programs have been established. OBJECTIVE: To recommend a standardized follow-up program of patients with AFX and PDS based on nationwide long-term estimates of local recurrence and metastasis. METHODS: All patients with AFX and PDS in Denmark between 2002 and 2022 were included. Danish National Registries were used to estimate the risks of local recurrence and metastasis for AFX and PDS. RESULTS: The 5-year risk of local recurrence was 10% for AFX and 17% for PDS. The 5-year risk of metastasis was 0.8% for AFX and 16% for PDS. PDS metastasized within 3 years in >90% of the patients with the lungs as the primary metastasis site (50%). Invasion beyond the subcutis, perineural/intravascular infiltration, and increasing age significantly increased the risk of PDS relapse. LIMITATIONS: Risk of misclassification and lack of detailed surgical information. CONCLUSION: The follow-up of patients with AFX can be limited to clinical visits for 4 years. Patients with PDS should be followed with clinical visits and PET/CT twice a year for the first 3 years and once a year for a minimum of 1 year.

Eyelid atypical fibroxanthoma: a rare challenging entity.

Atypical fibroxanthoma (AFX) is a rare neoplasm, with a limited number of cases reported in the periocular region. In this case report, we detail a 63-year-old woman who presented with a polypoid, exophytic lesion on her right upper eyelid that had been progressing for a year. The lesion was meticulously excised with security margins and reconstructed using a glabellar flap. Following a thorough microscopic and immunohistochemical analysis, AFX was diagnosed. Despite its sometimes clinical and histological benign appearance, AFX is classified as a malignant neoplasm; however, it carries an excellent prognosis with low metastasis and recurrence rates. Complete excision with safety margins is essential and an adequate post-operative surveillance is recommended. Owing to its rarity, ophthalmologists should remain vigilant and include AFX in their differential diagnosis, as the tumor's benign appearance may lead to misdiagnosis of this malignant entity.

La presencia de infiltración linfovascular y de un alto número de mitosis se asocia a un mayor riesgo de recidiva en sarcoma pleomórfico dérmico / Lymphovascular Invasion and High Mitotic Count Are Associated With Increased Risk of Recurrence in Pleomorphic Dermal Sarcoma

Introducción y objetivo El fibroxantoma atípico (FXA) y el sarcoma pleomórfico dérmico (SPD) son neoplasias de origen mesenquimal poco frecuentes. Debido a la baja incidencia del SPD y a una nomenclatura históricamente confusa existe poca información acerca de la verdadera agresividad de este tumor. Realizamos el presente estudio con el objetivo de identificar qué características clínicas y/o histológicas del SPD son predictoras de riesgo de recidiva. Material y método Se diseñó un estudio bicéntrico observacional retrospectivo de 31 casos de SPD diagnosticados y tratados en el Hospital Clínico Universitario de Valencia y el Instituto Valenciano de Oncología, entre los años 2005 y 2020. Se realizó un análisis descriptivo de las características clínicas e histológicas, un análisis inferencial univariado y un análisis multivariado mediante la regresión de Cox. Resultados En el análisis univariado, la recidiva tumoral (p<0,001), la necrosis (p=0,020), la infiltración linfovascular (p=0,037), la infiltración perineural (p=0,041) y el número de mitosis (categorizado en categorizado en <18 y ≥18 por 10 campos de gran aumento) (p=0,093), se asociaron a una menor supervivencia libre de enfermedad. En el análisis multivariado, el número de mitosis (categorizado en <18 y ≥18) y la infiltración linfovascular (p<0,05) se asociaron a una menor supervivencia libre de enfermedad. Conclusión El SPD es un tumor agresivo, en el que la presencia de un alto recuento mitótico (≥18) y/o invasión linfovascular se asocian a un mayor riesgo de recidiva y a una peor supervivencia libre de enfermedad. La necrosis y la infiltración perineural, también son hallazgos que probablemente se asocien a una mayor agresividad tumoral (AU)

Background and objective Atypical fibroxanthoma and pleomorphic dermal sarcoma (PDS) are rare mesenchymal tumors. Due to the low incidence of PDS and a historically confusing nomenclature, little is known about the true aggressiveness of this tumor. The aim of this study was to investigate clinical and histologic risk factors for recurrence in PDS. Material and methods Retrospective, observational, bicentric study of 31 PDSs diagnosed and treated at Hospital Clínico Universitario de Valencia and Instituto Valenciano de Oncología in Valencia, Spain, between 2005 and 2020. We described the clinical and histologic features of these tumors and performed univariate analysis and multivariate Cox regression analysis. Results In the univariate analysis, tumor recurrence (P<.001), necrosis (P=.020), lymphovascular invasion (P=.037), perineural invasion (P=.041), and mitotic count (<18 vs ≥18 mitoses per 10 high-power fields) (P=.093) were associated with worse disease-free survival. In the multivariate Cox regression analysis, mitotic count and lymphovascular invasion retained their significance as predictors of worse disease-free survival (P<.05). Conclusions PDS is an aggressive tumor in which a high mitotic count (≥18) and lymphovascular invasion are associated with a higher risk of recurrence and worse disease-free survival. Necrosis and perineural invasion are also probably linked to increased tumor aggressiveness (AU)

[Translated article] Lymphovascular Invasion and High Mitotic Count Are Associated With Increased Risk of Recurrence in Pleomorphic Dermal Sarcoma / La presencia de infiltración linfovascular y de un alto número de mitosis se asocia a un mayor riesgo de recidiva en el sarcoma pleomórfico dérmico

Background and objective Atypical fibroxanthoma and pleomorphic dermal sarcoma (PDS) are rare mesenchymal tumors. Due to the low incidence of PDS and a historically confusing nomenclature, little is known about the true aggressiveness of this tumor. The aim of this study was to investigate clinical and histologic risk factors for recurrence in PDS. Material and methods Retrospective, observational, bicentric study of 31 PDSs diagnosed and treated at Hospital Clínico Universitario de Valencia and Instituto Valenciano de Oncología in Valencia, Spain, between 2005 and 2020. We described the clinical and histologic features of these tumors and performed univariate analysis and multivariate Cox regression analysis. Results In the univariate analysis, tumor recurrence (P<.001), necrosis (P=.020), lymphovascular invasion (P=.037), perineural invasion (P=.041), and mitotic count (<18 vs ≥18 mitoses per 10 high-power fields) (P=.093) were associated with worse disease-free survival. In the multivariate Cox regression analysis, mitotic count and lymphovascular invasion retained their significance as predictors of worse disease-free survival (P<.05). Conclusions PDS is an aggressive tumor in which a high mitotic count (≥18) and lymphovascular invasion are associated with a higher risk of recurrence and worse disease-free survival. Necrosis and perineural invasion are also probably linked to increased tumor aggressiveness (AU)

Introducción y objetivo El fibroxantoma atípico (FXA) y el sarcoma pleomórfico dérmico (SPD) son neoplasias de origen mesenquimal poco frecuentes. Debido a la baja incidencia del SPD y a una nomenclatura históricamente confusa existe poca información acerca de la verdadera agresividad de este tumor. Realizamos el presente estudio con el objetivo de identificar qué características clínicas y/o histológicas del SPD son predictoras de riesgo de recidiva. Material y método Se diseñó un estudio bicéntrico observacional retrospectivo de 31 casos de SPD diagnosticados y tratados en el Hospital Clínico Universitario de Valencia y el Instituto Valenciano de Oncología, entre los años 2005 y 2020. Se realizó un análisis descriptivo de las características clínicas e histológicas, un análisis inferencial univariado y un análisis multivariado mediante la regresión de Cox. Resultados En el análisis univariado, la recidiva tumoral (p<0,001), la necrosis (p=0,020), la infiltración linfovascular (p=0,037), la infiltración perineural (p=0,041) y el número de mitosis (categorizado en categorizado en <18 y ≥18 por 10 campos de gran aumento) (p=0,093), se asociaron a una menor supervivencia libre de enfermedad. En el análisis multivariado, el número de mitosis (categorizado en <18 y ≥18) y la infiltración linfovascular (p<0,05) se asociaron a una menor supervivencia libre de enfermedad. Conclusión El SPD es un tumor agresivo, en el que la presencia de un alto recuento mitótico (≥18) y/o invasión linfovascular se asocian a un mayor riesgo de recidiva y a una peor supervivencia libre de enfermedad. La necrosis y la infiltración perineural, también son hallazgos que probablemente se asocien a una mayor agresividad tumoral (AU)

Clinical and Dermoscopic Characteristics of Cutaneous Sarcomas: A Literature Review.

Under the umbrella of cutaneous sarcomas (CS) we include a heterogeneous group of rare, malignant, mesenchymal neoplasia, such as dermatofibrosarcoma protuberans, atypical fibroxanthoma, cutaneous undifferentiated pleomorphic sarcoma, cutaneous angiosarcoma and leiomyosarcoma. Clinical presentation and histopathological examination are the cornerstone of CS diagnosis and classification. There are scarce data in the literature in regards to the clinical and dermatoscopic characteristics of CS and the role of dermatoscopy in their early identification. We performed a literature review, aiming to summarize current data on the clinical and dermatoscopic presentation of the most common types of cutaneous sarcomas that may facilitate early diagnosis and prompt management. Based on the available published data, CS are characterized by mostly unspecific dermatoscopic patterns. Dermatofibrosarcoma protuberans, Kaposi's sarcoma, and in a lesser degree, cutaneous angiosarcoma, may display distinct dermatoscopic features, facilitating their early clinical recognition. In conclusion, dermatoscopy, in conjunction with the overall clinical context, may aid towards suspicion of CS.