Pleomorphic Dermal Sarcoma Research Articles

Mohs Micrographic Surgery and Wide Local Excision in Pleomorphic Dermal Sarcoma on a National Scale.

Mohs Micrographic Surgery and Wide Local Excision in Pleomorphic Dermal Sarcoma on a National Scale.

T-cell Clonality in Pleomorphic Dermal Sarcoma in Male Veterans: A Report of 2 Cases and a Review of the Literature.

The standard treatment of choice for pleomorphic dermal sarcoma (PDS), a relatively uncommon soft tissue sarcoma and 1 morphologically similar to atypical fibroxanthoma, is wide local excision with close clinical follow-up. Studies regarding management of advanced/metastatic PDS with immune checkpoint inhibitors are limited as most STSs have historically been viewed as being immunologically inert. Contradicting this belief, in this report, we describe 2 cases of PDS with a robust host response. Histopathology of both cases revealed a dermal neoplasm comprising mitotically active, pleomorphic, spindled-to-ovoid cells, which were immunohistochemically negative for keratinocytic, melanocytic, and smooth muscle markers. An unusual feature in both cases was the presence of a brisk host response. Additional workup of the infiltrating lymphocyte population revealed an abnormal CD4:CD8 ratio in both cases, with the proportion of CD8+ lymphocytes surpassing (case 1) and equaling (case 2) that of the CD4+ T-lymphocyte population. The increased proportion of CD8+ lymphocytes prompted the additional workup of TCR gene rearrangement, which revealed a clonal population of T lymphocytes in both cases. The robust and clonal T-lymphocyte host response in both of our cases suggests that PDS appears to fit the classic model of an inflammatory-type tumor and may be a candidate for checkpoint inhibition. Future work includes additional reports of cases of PDS with an infiltrating clonal T-lymphocyte population and detailing the function and specificity of the infiltrating T lymphocytes to ascertain whether they have the potential to recognize and lyse the tumors they colonize.

The incidence of atypical fibroxanthoma and pleomorphic dermal sarcoma in Denmark from 2002 to 2022

BackgroundThe purpose of this study was to assess trends in the incidence rates and overall survival of atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) in the Danish population from 2002 to 2022. MethodsWe included all patients diagnosed with AFX or PDS in the Danish National Pathology Register (DNPR) during the study period. We computed the age-adjusted incidence rate (AAIR) per 100,000 and the average annual percent change (AAPC) and developed an age-period-cohort (APC) model of incidence. ResultsWe included a total of 1118 patients, 78.3 % of whom were men. The median age upon diagnosis for AFX and PDS was 77.6 and 78.4 years, respectively. 84.5 % of the 1118 patients received an AFX diagnosis, while 15.5 % received a PDS diagnosis. The AAIR rose from 0.2 per 100,000 individuals in 2002 to 0.5 per 100,000 by 2022, with a peak increase of 0.75 per 100,000 in 2014. The AAPC for both tumors was 5.3 (95 % CI 2.9 %–7.7 %). We found a significant difference in overall survival between AFX and PDS, with PDS having worse overall survival than AFX. ConclusionThis study, which included the largest non-selected national population to date, found a significant increase in the incidence of AFX and PDS between 2002 and 2015, followed by a decrease.

Rare Intravascular Involvement of Pleomorphic Dermal Sarcoma Seen During Mohs Micrographic Surgery.

Pleomorphic dermal sarcoma (PDS) and atypical fibroxanthoma (AFX) are rare mesenchymal tumors that share similar clinical, histological, and immunohistochemical characteristics. Careful histopathological examination of a biopsy specimen that includes subcutaneous fat remains the preferred way to differentiate between these tumors. AFX is limited to dermal invasion, whereas PDS demonstrates deeper invasion. Moreover, PDS may present with tumor necrosis and high-grade histological findings, such as lymphovascular and perineural invasion, features absent in AFX. However, like PDS, AFX is a diagnosis of exclusion, and an exhaustive immunohistochemistry panel is recommended to distinguish these tumors from other spindled cell tumors in the differential diagnosis. The authors present the case of an 86-year-old man with biopsy-suspected AFX who was referred for Mohs micrographic surgery for tumor excision. During Mohs, the tumor was observed to have invaded deeply into the subcutaneous tissue and galeal aponeurosis, aligning more closely with a PDS. The diagnosis of PDS was confirmed using en face processing during Mohs surgery, which captured the intravascular involvement of a solitary vessel. Differentiating between PDS and AFX is important because PDS is a more aggressive tumor, with a higher rate of local recurrence and metastasis, and requires closer monitoring.

WP3.2 - Craniectomy With Soft Tissue Reconstruction for Locally Advanced Non-Melanoma Skin Cancer of Scalp with Calvarial Invasion: the Nottingham experience

Abstract Introduction Locally advanced non-melanoma skin cancer (NMSC) involving the periosteum or calvarium remain clinically challenging for patients unfit for immunotherapy due to medical comorbidities and/or frailty. This case series aims to explore outcomes for patients that underwent craniectomy and soft tissue reconstruction. Method Patients underwent craniectomy and soft tissue reconstruction for invasive NMSC with calvarium or periosteal invasion from 2016 to 2022 were included. Data including demographics, operative details, and clinical outcomes were sourced from Nottingham University Hospitals digital health record and the histopathology electronic database. Result 8 patients (Age: 78.4, 3F 5M) with significant comorbidities and varying degrees of periosteal or bone invasion fulfilled the inclusion criteria. These included four squamous cell carcinoma, two basal cell carcinoma and two pleomorphic dermal sarcomas. Five patients had a history of prior incomplete deep margin excision. The median soft tissue defect, tumour and bone defect size was 51.83cm2, 34.63cm2 and 42.25cm2 respectively. Intraoperative complications included one dural tear. Four patients underwent local flap reconstruction and with split thickness skin grafting, four patients underwent free flap reconstruction. Adjuvant radiotherapy was administered to three. Complications comprised partial graft loss in two and complete graft loss in one. There was partial flap loss in one case. One patient required subsequent parotidectomy due to regional progression before achieving disease control. All patients achieved lasting locoregional disease control (average follow up 29.7 months). Conclusion Craniectomy with soft tissue reconstruction is a safe and effective treatment option in advanced NMSC of the scalp in patients unsuitable for immunotherapy due to frailty or medical co-morbidity.

52336 The Use of Mohs Micrographic Surgery in Pleomorphic Dermal Sarcoma

52336 The Use of Mohs Micrographic Surgery in Pleomorphic Dermal Sarcoma

54853 Trends in Incidence and Mortality of Pleomorphic Dermal Sarcoma: A Retrospective Cohort Study Using SEER Data

54853 Trends in Incidence and Mortality of Pleomorphic Dermal Sarcoma: A Retrospective Cohort Study Using SEER Data

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.

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.

Proteomic analysis of pleomorphic dermal sarcoma reveals a fibroblastic cell of origin and distinct immune evasion mechanisms

Pleomorphic dermal sarcomas are infrequent neoplastic skin tumors, manifesting in regions of the skin exposed to ultraviolet radiation. Diagnosing the entity can be challenging and therapeutic options are limited. We analyzed 20 samples of normal healthy skin tissue (SNT), 27 malignant melanomas (MM), 20 cutaneous squamous cell carcinomas (cSCC), and 24 pleomorphic dermal sarcomas (PDS) using mass spectrometry. We explored a potential cell of origin in PDS and validated our findings using publicly available single-cell sequencing data. By correlating tumor purity (TP), inferred by both RNA- and DNA-sequencing, to protein abundance, we found that fibroblasts shared most of the proteins correlating to TP. This observation could also be made using publicly available SNT single cell sequencing data. Moreover, we studied relevant pathways of receptor/ligand (R/L) interactions. Analysis of R/L interactions revealed distinct pathways in cSCC, MM and PDS, with a prominent role of PDGFRB-PDGFD R/L interactions and upregulation of PI3K/AKT signaling pathway. By studying differentially expressed proteins between cSCC and PDS, markers such as MAP1B could differentiate between these two entities. To this end, we studied proteins associated with immunosuppression in PDS, uncovering that immunologically cold PDS cases shared a “negative regulation of interferon-gamma signaling” according to overrepresentation analysis.

Metastatic Pleomorphic Dermal Sarcoma Involving Tonsil and Thyroid: An Unusual Presentation

Metastatic Pleomorphic Dermal Sarcoma Involving Tonsil and Thyroid: An Unusual Presentation

Abstract 5094: Immunotherapy in advanced cutaneous non-melanomatous spindle cell neoplasms

Abstract Background: Non-melanomatous cutaneous spindle cell neoplasms (NMCSpC) are a rare group of malignancies including pleomorphic dermal sarcoma (PDS) and spindle-cell cutaneous squamous cell carcinoma (SpSCC). They present a diagnostic challenge with overlapping morphological features and variable patterns of immunohistochemical (IHC) staining. There is a lack of consensus on how to best manage advanced NMCSpC and limited reports of immunotherapy (IO) responses. This study reviews the efficacy of IO in NMCSpC and performs comprehensive tumor profiling to identify biological rationale for IO use in this rare group of tumors. Methods: We performed a single-center retrospective review of all locally-advanced or metastatic NMCSpCs treated with IO. Blinded histopathology reviews occurred to confirm each diagnosis. Overall response rates (ORR) were collected as per Response Evaluation Criteria in Solid Tumors 1.1 or Positron Emission Tomography Response Criteria 1.0. Comprehensive tumor profiling included whole exome sequencing for tumor mutational burden (TMB) and ultraviolet(UV)-signatures, and IHC for immune-cell infiltration (CD103/CD4/CD3/CD8/CD20) and immune-checkpoint expression (PD-L1/TIGIT/LAG3). Results: 7 patients were identified. Median follow up was 18.1 months (range: 5.3-34.7). ORR 86% (6/7) with five complete responses (CR). One patient who achieved stable disease progressed. Responses were durable with two patients in CR >30 months after IO commencement. Blinded pathological review identified 3 SpSCC, 2 PDS and 2 spindle cell tumors of unclear sub-classification. All patients had high TMB and UV-signatures. One patient had PD-L1 100% (combined positive score) with abundant immune-cell infiltration and LAG3 expression (Table 1). Conclusion: In advanced NMCSpC, excellent responses to IO with durable disease control was observed. IO is worthy of further exploration in these patients. UV-signatures and high TMB could be used to help select patients for treatment. Immunohistochemistry (IHC)^, tumor mutational burden and ultraviolet signatures Patient T-cell markers B-cell marker Immune-checkpoints Tumor mutational burden (mutations/megabase) Ultraviolet-mutational signature Best response assessment# CD103 CD4 CD3 CD8 CD20 PD-L1 TIGIT LAG3 1 1 20 1 1 0 7 0 0 17.94 Yes Stable metabolic response 2 1 20 30 10 0 100 0 10 35.34 Yes Complete metabolic response 3 1 10 10 5 0 5 0 0 104.87 Yes Complete metabolic response 4 1 0 1 0 0 0 0 0 74.04 Yes Partial metabolic response 5* NA NA NA NA NA NA NA NA 29 Yes Complete metabolic response 6 1 0 0 5 0 0 0 4 12.02 Yes Complete metabolic response 7 1 0 5 1 0 0 0 0 41.17 Yes Complete response ^IHC scores are % of positively stained cells, except for PD-L1 which is combined positive score (CPS). *Insufficient tissue for IHC on Patient 5. #As per PERCIST 1.0 on FDG-PET/CT or RECIST1.1 on CT. Citation Format: Luke S. McLean, Annette M. Lim, Christopher Angel, Richard J. Young, Angela Pizzolla, Stuart Archer, Alesha A. Thai, Benjamin Solomon, Jeremy Lewin, Danny Rischin. Immunotherapy in advanced cutaneous non-melanomatous spindle cell neoplasms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5094.

Progression of Atypical Fibroxanthoma to Metastatic Pleomorphic Dermal Sarcoma in a Lung Transplant Recipient

Introduction: Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare cutaneous malignancies often seen in elderly patients with photodamaged skin. Although solid organ transplant recipients (SOTRs) with AFX/PDS appear to have worse outcomes than the general population, the risk of progression from AFX to PDS in this group is not well studied. We present the case of a lung transplant patient with AFX recurring as PDS. Case Presentation: A 68-year-old male lung transplant patient with an extensive history of skin cancer presented with a 9-millimeter erythematous papule on the right vertex scalp. Biopsy revealed AFX, and the tumor cleared with 1 stage of MMS. Seven months later, the patient developed a rapidly growing, hemorrhagic nodule at the site, which was diagnosed as PDS. Despite initial treatment with doxorubicin, pazopanib, and radiation to the lung, liver, and bone lesions, the patient’s disease progressed. The patient was started on pembrolizumab with prednisone to mitigate the risk of organ rejection but succumbed to pneumonia with septic shock and respiratory failure. Discussion: Transplant patients have an increased risk of poor outcomes related to PDS. ICIs may be considered in advanced cases in which other treatment options have been exhausted. In conclusion, SOTRs with AFX/PDS should be aggressively treated and monitored as their risk of unfavorable outcomes appears to be increased.

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

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. 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 7years (2013-2019) to evaluate the use of HCTZ, immunosuppressive medication, second malignancies, and presence of diabetes mellitus. 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. 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 0.6cm × 0.6cm, 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 30days. The patient was directed to use this combination 5days per week for 6weeks. 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, 1.0cm × 0.9cm, amidst erythema. A subsequent incisional biopsy with histopathology and stains for CD10 and CD99, 3weeks 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: a case report

A pleomorphic dermal sarcoma (PDS) is considered a rare and poorly understood neoplasm of the skin.1 This has features similar to atypical fibroxanthoma (AFX).1 As well as the baseline similar characteristics to an AFX, a PDS also exhibits features of an infiltrative growth pattern which allows invasion of the subcutis, tumour necrosis and the possibility of lymphovascular invasion.2 These are more aggressive features than the more extensively reported AFX. There is a degree of metastatic potential associated with a PDS and hence early diagnosis and management with the appropriate multi-disciplinary team (MDT) is important to optimise the clinical prognosis. This case report will discuss a relatively rare diagnosis of a patient presenting with a PDS on the scalp and his management within the Oral and Maxillofacial Surgical (OMFS) Department, including consideration of his overall palliative care. Here, we will discuss the social, medical and physical implications of this diagnosis as well as considering the overall determinants of his quality of life (QoL).

Multidisciplinary management of pleomorphic dermal sarcoma of the scalp: A single institution study

BackgroundPleomorphic dermal sarcoma (PDS) of the scalp is a rare cutaneous malignancy, the location of which creates unique technical and cosmetic obstacles. Optimal management is not defined. We reviewed our institution’s approach and outcomes for this entity. Materials & methodsBetween 2000–2020, 15 patients with scalp PDS were evaluated and treated at our multidisciplinary sarcoma center. Patient characteristics, treatment approach, and outcomes were analyzed. ResultsThirteen patients (87%) presented with primary disease alone, one (7%) presented with recurrent disease after initial resection, and one (7%) presented with synchronous primary and metastatic disease. Radiation therapy (RT) was recommended in 10 patients (67%) and completed in 8 (53%) (3 preoperative, 5 postoperative). Eight patients (53%) underwent staged plastic surgery complex wound closure. Thirteen patients were alive without disease, one was alive with disease, and one was deceased with known recurrent disease at time of last follow-up. ConclusionLimited data are available to guide management of scalp PDS. Due to possible need for staged plastic surgery closure to ensure negative margins and optimize wound healing, initiation of postoperative RT may be delayed. Future multi-institutional study is required to further define the extent of surgery and role and timing of RT.

Pathophysiology, Histopathology, and Differential Diagnostics of Basal Cell Carcinoma and Cutaneous Squamous Cell Carcinoma-An Update from the Pathologist's Point of View.

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequently occurring non-melanocytic skin cancers. The objective of our study is to present the pathophysiology of BCC and cSCC and its direct relationship with the histopathological diagnostics and the differential diagnostics of these types of cancer, based on the morphological characteristics, immunohistochemical profile, and genetic alterations. The qualitative study was based on emphasizing the morphological characteristics and immunohistochemistry profiles of BCC and cSCC and the differential diagnostics based on the tissue samples from the Clinical Pathology Department of Mures Clinical County Hospital between 2020 and 2022. We analyzed the histopathological appearances and immunohistochemical profiles of BCC and cSCC in comparison with those of Bowen disease, keratoacanthoma, hyperkeratotic squamous papilloma, metatypical carcinoma, pilomatricoma, trichoblastoma, Merkel cell carcinoma, pleomorphic dermal sarcoma (PDS), and melanoma. Our study showed the importance of the correct histopathological diagnosis, which has a direct impact on the appropriate treatment and outcome for each patient. The study highlighted the histopathological and morphological characteristics of NMSCs and the precursor lesions in HE and the immunohistochemical profile for lesions that may make the differential diagnosis difficult to establish.

Surgical Approach of Pleomorphic Dermal Sarcoma on the Scalp: A Case Report

Pleomorphic dermal sarcoma (PDS) is a fast-growing mesenchymal tissue tumor with similar characteristics to an atypical fibroxanthoma (AFX) presenting a significant clinical challenge to diagnose for physicians. We report a 79-year-old male presenting with a 3-month history of a lesion on his scalp that had been previously superficially biopsied yielding a diagnosis of PDS or AFX. Following a second biopsy, new findings led to the diagnosis of PDS. A wide local excision with 2 cm margin with delayed split-thickness skin graft reconstruction was performed. Treatment for PDS favors wide local excision with a 2–3 cm margin and adjuvant radiotherapy if perineural involvement. We support the following recommendations: full-thickness appropriate tissue diagnosis, pulmonary computed tomography scan, or X-ray to rule out metastasis, followed by a multidisciplinary team evaluation. These complex cases should be presented at a tumor board and tailored treatments should be based on patient risk factors and relevant history.

A-245 - Clinical characteristics and surgical approach of patient with SAMPUS/ Melanoma and pleomorphic dermal sarcoma on face

A-245 - Clinical characteristics and surgical approach of patient with SAMPUS/ Melanoma and pleomorphic dermal sarcoma on face