Pleomorphic Dermal Sarcoma Research Articles

Lethal Dermal Sarcoma in Immunosuppressed Patients.

Skin cancer is the leading malignancy in immunosuppressed patients, including organ transplant recipients (OTRs), which is increasing in incidence as OTRs live longer. We performed a single-center case series of 4 patients with scalp pleomorphic dermal sarcoma and a history of multiple keratinocyte carcinomas. Outcomes included incidence of dermal sarcoma, dermal sarcoma-related mortality, and histopathologic findings. Out of more than 200 patients followed over a 3-year period in Massachusetts General Hospital High Risk Skin Cancer Clinics, all skin cancer-related deaths (2/2) were due to metastatic dermal sarcoma. Three of 4 patients diagnosed with scalp dermal sarcoma were OTRs and had been on at least one immunosuppressive medication for a median of 9 years. For patients who died from dermal sarcoma, the median time between diagnosis and death was 6 months. Our findings suggest pleomorphic dermal sarcoma contributes to skin cancer-related morbidity and mortality in OTRs.

Histopathological and Immunohistochemical Appearance of Pleomorphic Dermal Sarcoma

Pleomorphic dermal sarcoma is a rare and aggressive entity that originates in the skin’s dermis. This poorly defined tumor usually appears on the sun exposed skin of the elderly and involves the male gender more often. We describe the case of a 54 year old male patient who presented to the Surgery Department with a tumor located on the scalp. Surgery was performed and the sample was sent to the Pathology Department of Mures Clinical County Hospital for further analysis. Histological analysis showed a tumor with solid architecture and nesting phenomenon, composed of pleomorphic epithelioid cells with high atypia. Typical and atypical mitoses were observed. Immunohistochemistry showed positivity for the following markers: vimentin, CD68 and ki67- proliferation value of 90%. The cells were negative to CK AE1/AE3, S100, SOX10, HMB45, MelanA, CD31, Desmin and SMA. In conclusion, pleomorphic dermal sarcoma represents a challenging diagnosis. The case highlights the histological and immunohistochemistry appearance of the neoplasm. Due to the local aggressivity, difficulty in providing negative resection margins and uncertain prognosis, it’s important to take this entity into consideration each time we encounter a cutaneous pleomorphic tumor.

Oncological Safety and Recurrence in the Surgical Treatment of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma of the Scalp.

Simple SummaryAtypical fibroxanthoma and pleomorphic dermal sarcoma represent two tumors on the spectrum of a rare dermal sarcoma entity. Close clinical presentation and nearly identical histologic features but distinct prognoses make proper treatment strategies challenging. We performed a retrospective analysis of 32 patients with AFX or PDS in the scalp to provide guidance regarding the extent of radical excision to achieve stable oncological outcomes and whether radical tumor resection on the scalps required complex soft-tissue reconstruction. Compared to AFX, PDS shows a more aggressive growth pattern with frequent satellite metastases and distant metastases. These require extensive resections for local control to achieve long-term remission in most PDS patients. Despite the limited elasticity of the scalp, plastic reconstructive procedures can obtain reliable soft tissue reconstruction, even for complete scalp defects. Due to their rarity, managing these tumors requires an interdisciplinary setting in a specialized sarcoma center.Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are two distinct designations for a rare dermal sarcoma entity. These tumors arise predominantly in the sun-damaged skin of elderly patients. Although both AFX and PDS have a similar clinical presentation and nearly identical genetic features, they significantly differ in prognosis. Here we present a retrospective single-center chart review analyzing the outcomes of patients treated for dermal sarcoma. The radicality of the tumor-resection extent and soft-tissue reconstructive options were assessed. Patients between January 2010 and August 2021 were included. We recorded resection margins, tumor recurrence, overall survival, number of operations until complete tumor resection, and reconstructive procedures; any complications were recorded. Furthermore, we analyzed a subgroup of patients with satellite metastases. A total of 32 patients met the inclusion criteria (30 male, 2 female, median age of 77.5 years (interquartile range (IQR) 74–81)). Histopathology revealed AFX in 14 patients and PDS in 18 patients. Margin-free resection was achieved in 31 cases, and 27 patients were remission free over the reported period. The local recurrence rate was 5, and distant metastasis was detected in four cases. Of all the PDS cases, nine presented with satellite metastasis. No AFX had satellite metastases. Due to their rarity, managing these tumors requires an interdisciplinary setting in a specialized sarcoma center.

Pleomorphic Dermal Sarcoma Does Not Represent an Entity Different From Atypical Fibroxanthoma.

Pleomorphic Dermal Sarcoma Does Not Represent an Entity Different From Atypical Fibroxanthoma.

Risk factors for local atypical fibroxanthoma recurrence and progression to pleomorphic dermal sarcoma: A meta-analysis of individualized participant data.

BackgroundRisk factors for local atypical fibroxanthoma (AFX) recurrence and progression to pleomorphic dermal sarcoma (PDS) have not previously been identified.ObjectiveTo identify risk factors and provide follow‐up suggestions for local AFX recurrence and progression to PDS.Methods and MaterialsA literature search was performed in the PubMed, EMBASE, and Cochrane databases. The PRISMA and MOOSE guidelines were followed. The risks of local AFX recurrence and progression to PDS were presented as Kaplan–Meier plots and risk factors were presented as hazard ratios (HRs) calculated with univariate and multivariate Cox regression.ResultsFive hundred and ninety‐eight patients with AFX from 14 studies were included. Age >74 years and male sex significantly increased the risk of local recurrence (HR: 7.31 [95% confidence interval [CI]: 1.78–30.0], p < 0.01 and HR: 2.89 [95% CI: 1.04–8.01], p < 0.05, respectively). There was no difference when comparing wide local excision and Mohs' micrographic surgery (p = 0.89). The risks of local AFX recurrence and progression to PDS after 2 years were <1%.ConclusionA more intensive follow‐up regimen could be considered in patients >74 years old and males due to the higher risk of local AFX recurrence.

Survival differences of low-grade versus high-grade head and neck pleomorphic dermal sarcomas and a review of a scalp case.

To examine survival by tumor grade of pleomorphic dermal sarcomas (PDS) of the head and neck (H&N) and review a scalp PDS case. Patients in the Surveillance, Epidemiology, and End Results (SEER) database were included from 1980 to 2016 based on a diagnosis of H&N PDS. Survival estimates were performed using Kaplan-Meier analysis. Additionally, a case of a grade III H&N PDS is presented. Two hundred-seventy cases of PDS were identified. The mean age at diagnosis was 75.1 years (SD: 13.5). Two hundred-thirty-four (86.7%) patients were male. Eighty-seven percent of patients received surgery as a part of their care. The 5-year overall survival rates for grades I, II, III, and IV PDSs were 69%, 60%, 50%, and 42%, respectively (P = 0.03). H&N PDS occurs most commonly in older-age males. Surgical management is frequently a part of H&N PDS care. Survival rates significantly decline based on tumor grade.

Hemato-Oncological Diseases as Risk Factor for Recurrence or Metastasis of Pleomorphic Dermal Sarcoma

BackgroundAtypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are increasingly common sarcomas of the skin with a genetic UV signature. Immunosuppression is a known risk factor for developing other UV-induced skin cancers such as cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), and Merkel cell carcinoma with increased mortality. In case reports or small case series of AFX/PDS patients, immunosuppression has been hypothesized as a risk factor for the development of distant metastases. The aim of the present study was to analyze immunosuppression as a risk factor for AFX/PDS in a large patient cohort.MethodsA cohort of 164 patients with AFX/PDS (47 AFX and 117 PDS) was collected between 2003 and 2021 and analyzed for clinicopathological data with a special focus on immunosuppression.ResultsOf all patients, 29.9% had any kind of immunosuppression; 6.4% of the AFX and 12.0% of the PDS patients had underlying hemato-oncological diseases. Patients with immunosuppression due to an underlying hemato-oncological disease had a significantly increased risk of progressing to (p = 0.010) and developing distant organ metastases (p = 0.000).ConclusionsImmunosuppression seems to be a risk factor for developing AFX/PDS with worse clinical outcomes. Therefore, immunosuppression, especially underlying hemato-oncological diseases, should be considered in the treatment and follow-up care of patients with AFX/PDS.

A review of Mohs micrographic surgery for skin cancer. Part 1: Melanoma and rare skin cancers.

Mohs micrographic surgery (MMS) is a precise and effective method commonly used to treat high-risk basal cell carcinoma and squamous cell carcinoma on the head and neck. Although the majority of evidence for MMS relates to keratinocyte cancers, there is published evidence for other types of skin cancer. This review aims to discuss the evidence for using MMS to treat six different types of skin cancer [malignant melanoma, lentigo maligna, dermatofibrosarcoma protuberans, atypical fibroxanthoma (AFX), microcystic adnexal carcinoma and pleomorphic dermal sarcoma (PDS)] particularly in the context of survival rates and cancer recurrence. These cancers were chosen because there was sufficient literature for inclusion and because MMS is most useful when cancers are contiguous, rather than for cancers with marked metastatic potential such as angiosarcoma or Merkel cell carcinoma. We searched MEDLINE, PubMed and Embase using the keywords: 'melanoma', 'mohs micrographic surgery', 'lentigo maligna', 'dermatofibrosarcoma protuberans', 'atypical fibroxanthoma', 'microcystic adnexal carcinoma' and 'pleomorphic dermal sarcoma' along with their appropriate synonyms, to identify the relevant English-language articles from 2000 onwards, given that literature for MMS on nonkeratinocyte cancers is sparse prior to this year. AMSTAR (A MeaSurement Tool to Assess systematic Review) was used to assess the validity of systematic reviews. Further high-quality, multicentre randomized trials are necessary to establish the indications and efficacy of MMS for rarer cancers, particularly for AFX and PDS, for which only limited studies were identified.

Atypical fibroxanthoma and pleomorphic dermal sarcoma: Is superficial infiltration in subcutaneous tissue acceptable in AFX?

BackgroundAtypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare cutaneous neoplasms forming a spectrum. Case reports with recurrences and metastasis have been published despite the current view that AFX is benign. The aim of this study was to identify clinical and histopathological features that predict tumor recurrence. MethodsA retrospective review of AFX and PDS cases was performed. Clinical characteristics were obtained from patient records. ResultsA total of 29 AFX and 23 PDS cases were identified. Review led to re-classification of 12 cases (18%). In 14/50 (26.9%) cases a recurrence occurred. Recurrences were significantly more likely to occur when the tumor showed any infiltration in the subcutaneous fat (100% vs 43.2%, p = 0.000) or when the tumor diameter exceeded 2 cm (46.2% vs 16.2%, p = 0.030). ConclusionsThis study shows that histopathological distinction between AFX and PDS remains difficult with reclassification in 12 out of 52 (18%) cases upon review. All AFX cases solely confined to the dermis behaved benign. We therefore advocate to classify all cases with any form of subcutaneous extension as PDS, and only lesions without as AFX. This contrasts with the current general opinion in which superficial subcutaneous invasion is still accepted in AFX.

S1-guideline atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS).

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare cutaneous neoplasms representing histomorphological, genetic as well as epigenetic variants of a disease spectrum. Both tumors typically manifest as nonspecific, often ulcerated, skin- to flesh-colored nodules in chronically sun-damaged skin of elderly male patients. AFX is a rather well demarcated, often rapidly growing tumor. PDS tumors are poorly circumscribed and are characterized by aggressive infiltrative growth. Fast as well as slow growth behavior has been reported for both tumors. Histologically, both are composed of spindle-shaped and epithelioid tumor cells with pleomorphic nuclei as well as atypical multinucleated giant cells. Atypical mitoses are common. In contrast to AFX, PDS involves relevant parts of the subcutis and shows areas of tumor necrosis and/or perineural infiltration. Due to the poorly differentiated nature of AFX/PDS (Grade3), histopathologically similar cutaneous sarcomas, undifferentiated carcinomas, melanomas and other diseases have to be excluded by immunohistochemical analysis. The treatment of choice is micrographically controlled surgery. In cases of AFX, a cure can be assumed after complete excision. Local recurrence rates are low as long as PDS tumors are surgically removed with a safety margin of 2cm. Metastasis is rare and mostly associated with very thick or incompletely excised tumors; it mainly affects the skin and lymph nodes. Distant metastasis is even more rare. No approved and effective systemic therapy has been established.

Four-Cell Population Collision Tumor of the Scalp: A Case Report and Review of Literature

Background: Most cases of collision tumors (CTum) usually present with 2 histologic cell types. We report a unique CTum case comprised of 4 cell populations. Additionally, we performed a systematic review of the current literature published on head and neck collision tumors (HNCTum). Methods: Eighty-one-year-old male presents with a scalp lesion of several years’ duration. PET/CT scan demonstrated increased uptake in the scalp. Wide local excision with free flap reconstruction was performed and tissue pathology reviewed. Database search of HNCTum was performed and reported. Results: Specimen histopathology consisted of melanoma, squamous cell carcinoma, basal cell carcinoma, and pleomorphic dermal sarcoma. Thirty-one articles met inclusion criteria: 11 thyroid, 7 cutaneous, 7 laryngeal, 2 lymph nodes, 2 salivary gland, 1 glottic, 1 maxillary sinus, and 1 tonsil. Conclusion: We present a highly unique CTum case of 4 different cell populations. The systematic review provides a comprehensive report of HNCTum in literature.

Clinicopathological and Genomic Profiles of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma Identify Overlapping Signatures with a High Mutational Burden.

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare tumors developing in chronically sun-exposed skin. Clinicopathological features are similar, but they differ in prognosis, while PDS has a more aggressive course with a higher risk for local recurrence and metastases. In current clinical practice, they are diagnosed by exclusion using immunohistochemistry. Thus, stringent diagnostic criteria and correct differentiation are critical in management and treatment for optimal outcomes. This retrospective single-center study collected clinicopathological data and tumor samples of 10 AFX and 18 PDS. Extracted genomic DNA from tumor specimens was analyzed by a next-generation sequencing (NGS) platform (FoundationOne-CDx™). Among 65 identified mutations, TP53 inactivating mutations were observed in all tumor specimens. In both AFX and PDS, the known pathogenic gene alterations in CDKN2A, TERT promoter, and NOTCH1 were frequently present, along with high mutational burden and stable Micro-Satellite Instability status. The mutational profiles differed only in ASXL1, which was only present in AFX. Further differences were identified in likely pathogenic and unknown gene alterations. Similarities in their genomic signatures could help to distinguish them from other malignancies, but they are not distinguishable between each other using the FoundationOne-CDx™ NGS panel. Therefore, histological criteria to determine diagnosis remain valid. For further insight, performing deep tumor profiling may be necessary.

PDGFB RNA in situ hybridization for the diagnosis of dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is a spindle cell neoplasm of the skin and superficial soft tissue with a tendency for locally aggressive behavior; metastatic potential coincides with fibrosarcomatous transformation. The vast majority of DFSPs harbor the t(17;22) translocation resulting in a COL1A1-PDGFB fusion that drives autocrine growth stimulation via PDGFB overexpression. Here, we examined the utility of PDGFB RNA chromogenic in situ hybridization (CISH) for the diagnosis of DFSP. A total of 337 tumors represented in whole tissue sections and tissue microarrays, including 37 cases of DFSP and 300 histologically similar spindle cell tumors, were subjected to PDGFB RNA CISH using commercially available probes. PDGFB overexpression was observed by light microscopy in 24 of 26 conventional DFSPs (92%) and 11 of 11 fibrosarcomatous DFSPs (100%). One of two DFSPs negative for PDGFB by RNA CISH was found to harbor an uncommon alternative rearrangement involving PDGFD. All examined cases of histologic mimics were negative for PDGFB overexpression; limited PDGFB expression, not reaching an empirical threshold of greater than 5 puncta or one aggregate of chromogen in more than 25% of cells, was observed in 7 of 300 mimics (2.3%), including desmoplastic melanoma, malignant peripheral nerve sheath tumor, angiosarcoma, and pleomorphic dermal sarcoma. Vascular PDGFB expression was seen in several tumor types. We conclude that PDGFB RNA CISH, with careful interpretation and the use of appropriate thresholds, may serve as a surrogate marker of PDGFB rearrangement and a useful ancillary tool for the diagnosis of DFSP.

COVID-19 impacts on dermatologic surgery patients: A single institution experience

COVID-19 impacts on dermatologic surgery patients: A single institution experience

Pleomorphic dermal sarcoma of the right acromion in a 59－year－old male patient

Pleomorphic dermal sarcoma of the right acromion in a 59－year－old male patient

18121 Undifferentiated pleomorphic dermal sarcoma with unusual keratoacanthoma-like clinical presentation

Background: Pleomorphic dermal sarcoma (PDS) is a rare malignant skin neoplasm. Here we present a patient with a PDS mimicking a keratoacanthoma (KA) in a patient with a history of multiple KAs.

Integrative Analysis of Pleomorphic Dermal Sarcomas Reveals Fibroblastic Differentiation and Susceptibility to Immunotherapy.

Pleomorphic dermal sarcoma (PDS) is a rare malignant cutaneous tumor with an unknown cell of origin. Locally defined tumors can be treated by curative excisions, whereas advanced stages of the disease are difficult to treat, using standard regimens. We performed whole-exome sequencing on a cohort of 28 individuals and corresponding transcriptomic analysis on 21 patients, as well as quantitative IHC image analysis on 27 patients. PDS exhibits a universally high mutational load (42.7 mutations/mega base) with an inflamed, immunogenic tumor microenvironment. Three cases of PDS showed response to immune checkpoint blockade. Local mutation rate variation together with mRNA expression data demonstrate that PDS form a distinct entity, with PDGFRB as a lineage marker. In addition, we found that PDS is of mesenchymal, fibroblastic differentiation. PDS is of fibroblastic differentiation and exhibits a strong susceptibility to immunotherapy, including a high mutational burden and an inflamed tumor microenvironment.

S3057 Upper Gastrointestinal Bleeding Secondary to Gastric Metastasis of Pleomorphic Dermal Sarcoma

INTRODUCTION: Pleomorphic dermal sarcoma (PDS) is a rare cutaneous malignancy, seen primarily in sun exposed areas of elderly individuals. Along with atypical fibroxanthoma (AFX), it is believed to belong to a spectrum of malignant disorders arising from a similar fibrohistiocytic mesenchymal origin. Compared to AFX, PDS represents a more aggressive phenotype of disease with higher rates of recurrence and metastasis. CASE DESCRIPTION/METHODS: An 87-year-old male with a history PDS of the scalp with metastasis to the right humerus presented to the hospital with one week of melena. Pertinent past medical history included non-small cell lung cancer, chronic lymphocytic leukemia, melanoma, squamous and basal cell carcinoma of the skin. On presentation he was noted to be anemic with a hemoglobin of 6.8 g/dL and hematocrit of 22%. He was started on intravenous (IV) proton pump inhibitor (PPI) and underwent an esophagogastroduodenoscopy (EGD). Upon visualization of the stomach, four masses were identified along the greater curvature ranging between 1cm and 2.5cm in size, three of which were actively bleeding. Biopsies of these masses were obtained with cold biopsy forceps. No alternative source of bleeding was identified on exam. Following EGD, supportive measures were continued with IV PPI and packed RBC transfusions. Tissue histology of the gastric masses were consistent with a malignant spindle cell neoplasm, identical to that of the patient's known PDS. Additional imaging revealed new soft tissue lesions in the left hepatic lobe, right kidney, bladder and peritoneum. Given his diffusely metastatic disease, co-morbidities and frailty, therapeutic options were limited. He was deemed not an appropriate chemotherapy candidate and ultimately pursued hospice care. DISCUSSION: We present a case of upper gastrointestinal bleeding secondary to gastric metastasis of PDS. Metastasis occurs in approximately 10-20% of patients with PDS, most commonly involving the lungs and skin1. PDS had previously been classified as undifferentiated pleomorphic sarcoma or malignant fibrous histiocytoma. Under this nomenclature it has rarely been described to metastasize to the stomach and few cases have presented with gastrointestinal bleeding. This case contributes to the general understanding that the stomach can be a metastatic site for a wide variety of non-gastrointestinal cancers.Figure 1.: Proximal gastric body mass along the greater curvature.Figure 2.: Distal gastric body mass along the greater curvature.

Pleomorphic dermal sarcoma: a retrospective study of 16 cases in a dermato-oncology centre and a review of the literature.

Relatively little is known about the true aggressive potential of pleomorphic dermal sarcoma (PDS) or optimal management strategies. To describe the outcomes of 16 cases of PDS treated at our hospital (14 with modified Mohs micrographic surgery [M-MMS] and two with conventional surgery) and establish an adequate plan for management. We reviewed 16 PDS cases treated at our hospital between October 2007 and June 2019 and compared our results with the available evidence. In total, 69% of cases had recurred after initial conventional surgery, M-MMS led to local disease control in 83% of cases, and 19% of patients developed metastasis. Combining all published PDS cases with ours, we calculated an overall metastasis rate of 12%, and an overall recurrence rate of 35% after conventional surgery and 17% after M-MMS. PDS is more aggressive than previously estimated, with an overall metastatic rate of 12%. Despite high recurrence rates with previous conventional surgery (69%), M-MMS achieved a good rate of local disease control (83%). Given the potential aggressivity of PDS and the importance of clear surgical margins, M-MMS appears to be more adequate than conventional excision. Staging studies and close monitoring are warranted in PDS patients, for which we propose a management algorithm.

Pleomorphic dermal sarcoma: a clinical and histological review of 49 cases

Pleomorphic dermal sarcoma (PDS) is a rare mesenchymal neoplasm that shares histopathological features with atypical fibroxanthoma (AFX), but has additional features of deep invasion of the superficial subcutis, tumour necrosis, and vascular and perineural invasion, which confers a risk of local recurrence and metastases. To study the clinical and pathological spectrum more comprehensively, we retrieved 49 cases of pleomorphic dermal sarcoma from our departmental files. There was a strong male predominance (n=45). The mean (range) age at presentation was 80 (47-97) years. The tumours had a median (range) maximum dimension of 23.5 (5-75) mm. There was a strong predilection for the head and face (n=47), with the scalp (n=32) being the most common site. Ulceration was observed in 21 patients, tumour necrosis in seven, perineural infiltration in six, and lymphovascular invasion in two. CD10 was expressed in all cases. Smooth muscle actin was expressed in 15 and CD68 in 14. Follow up was available in 41 cases (mean (range) 22.4 (2-90) months). Six patients had local recurrences, despite all having originally undergone primary surgical resections and having reports of clear margins. Progressive metastatic disease was observed in one patient who died from their disease. Based on the Kaplan Meier method, median overall survival was 70.8 (8.4-133.1) months. Although AFX and PDS may be part of a spectrum, distinction is important to emphasise the potential for malignant behaviour in PDS.