Spontaneous regression of locally advanced pleomorphic dermal sarcoma of the forehead: a case report

Pleomorphic dermal sarcoma is a cutaneous soft tissue sarcoma that presents as a rapidly enlarging tumor, typically on a sun-exposed location of elderly individuals. The neoplasm shares many similar features - clinical, pathologic, immunohistochemical and genomic - with atypical fibroxanthoma. However, adverse histologic characteristics (deep subcutaneous invasion, tumor necrosis, lymphovascular invasion, and/or perineural invasion) differentiate pleomorphic dermal sarcoma from atypical fibroxanthoma and may account for the more aggressive biologic behavior of pleomorphic dermal sarcoma: local recurrence and metastases. The features of a woman with pleomorphic dermal sarcoma are described. Her sarcoma presented as a rapidly growing ulcerated red nodule on the left side of her face. Imaging studies were performed prior to surgery. The tumor was extirpated with a wide local excision and she received postoperative radiotherapy. There has been no recurrence or metastasis at one-year follow-up. Pleomorphic dermal sarcoma has previously been referred to as a malignant fibrous histiocytoma (until the term became antiquated) and an undifferentiated pleomorphic sarcoma. However, the latter term includes not only neoplasms from the skin but also sarcomas from internal organs, retroperitoneal and osteoid origin. Therefore, when classifying this undifferentiated soft tissue sarcomas of cutaneous origin, the term pleomorphic dermal sarcoma may be preferred.

Atypical fibroxanthoma and pleomorphic dermal sarcoma harbor frequent NOTCH1/2 and FAT1 mutations and similar DNA copy number alteration profiles

TERT promoter mutations are frequent in atypical fibroxanthomas and pleomorphic dermal sarcomas

BackgroundPleomorphic dermal sarcoma is the cutaneous variant of undifferentiated pleomorphic sarcoma. It is a rare malignancy of unclear histogenesis; it is a diagnosis of exclusion that requires extensive use of immunohistochemistry to rule out other malignancies. Pleomorphic dermal sarcoma typically presents as a solitary tumor in sun-exposed areas and may have unpredictable clinical behavior, with some tumors associated with metastasis and death.Case presentationWe present an unusual case of multifocal pleomorphic dermal sarcoma arising in the areas of alpha-1-antitrypsin deficiency panniculitis in a lung transplant patient. Our patient was a 58-year-old white woman whose initial presentation was consistent with alpha-1-antitrypsin deficiency panniculitis. She then developed extensive multifocal, bleeding, and ulcerated nodules in the areas of the panniculitis. A skin biopsy was consistent with a diagnosis of pleomorphic dermal sarcoma. Her immunosuppressive regimen was decreased, and she was treated with liposomal doxorubicin 40 mg/m2 every 3 weeks with some initial improvement in the size of her tumors. However, soon after beginning therapy, she developed pneumonia and septic shock and ultimately died from multi-organ failure.ConclusionsWe hypothesize that chronic, multifocal inflammation in the skin in the setting of immunosuppression led to simultaneous, malignant transformation in numerous skin lesions. We discuss the challenges of diagnosing pleomorphic dermal sarcoma, therapeutic options, and stress the need for multidisciplinary management of these cases.

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) tumors share many clinical, etiologic, and histologic features and likely represent components of a tumor spectrum. In dermatologic oncology, differentiating between AFX and PDS is pivotal as tumors with histological features consistent with PDS are more likely to behave in a clinically aggressive manner. Importantly, the term "pleomorphic dermal sarcoma" (PDS) is a more appropriate designation than "undifferentiated pleomorphic sarcoma" (UPS) for describing deeper, more aggressive, histologically high-grade cutaneous tumors that otherwise resemble AFX. Surgery remains the gold standard for treatment. In the setting of AFX, excision with the Mohs micrographic technique appears to offer superior tumor control rates while maintaining greater tissue preservation over wide local excision and should be considered first line. In the setting of PDS, optimal management is less clear given the paucity of available data. However, due to its greater propensity to recur and metastasize, extirpation with complete tumor margin control appears paramount. The roles of imaging and SLNB in management and clinical outcomes of AFX and PDS are unclear given the lack of available data. In reality, these tools are unlikely to be helpful in most cases of AFX. However, in the setting of PDS, emerging literature indicates that these tumors are inherently higher risk, and thus, imaging and SLNB may be helpful in select cases. Additionally, radiation therapy may be of adjuvant benefit for these tumors when clear surgical margins cannot be obtained. While traditional chemotherapy has been largely ineffectual, the recent discovery of key oncogenetic mutations has allowed for the identification of several potential molecular drug targets that may have a therapeutic role with future study. In the unfortunate setting of metastatic disease, a multidisciplinary approach is optimal. Further studies are needed to establish definitive conclusions regarding risk stratification and best management practices.

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.

Differentiating atypical fibroxanthoma (AFX) from pleomorphic dermal sarcoma (PDS) remains a challenge. Increasing the use of immunohistochemistry has led to the proposal of many immunomarkers that may aid in the diagnosis of AFX and PDS. In this meta-analysis, we investigate the immunohistochemical characteristics of AFX and PDS based on suggested immunomarkers in the literature. Second, we identify potential distinctive markers found in the tumors' respective immunohistochemical profiles. We included studies using immunomarkers on at least 10 consecutive patients with clinically and histopathologically verified AFX or PDS. The positive rates of the immunomarkers were pooled across the included studies with random-effects models. The immunomarkers were further categorized by a priori-chosen cutoffs in positive rates as positive markers (>90%) or negative markers (<10%). Differences between AFX and PDS were compared with Wald tests. We included 45 studies (1516 tumors) reporting on 35 immunomarkers. CD10 was positive in 94% (95% confidence interval, 87-99) of AFX cases and 100% (95% confidence interval, 99-100) of PDS cases. In accordance with the literature, both AFX and PDS were mainly negative for epithelial markers, melanocytic markers, markers of smooth muscle differentiation, and endothelial markers. None of the examined immunomarkers could distinguish AFX from PDS. Our results suggest that CD10 is a useful positive immunomarker for both AFX and PDS. We found no difference in immunohistochemical profile when comparing AFX with PDS. Our analysis suggests that CD10, AE1/AE3, CK5/CK6, p63, S100, SOX10, desmin, SMA, CD31, and ERG could be used to differentiate AFX and PDS from other spindle cell neoplasms.

BackgroundAtypical fibroxanthomas (AFX) and pleomorphic dermal sarcomas (PDS) are lesions of the skin with overlapping histologic features and unspecific molecular traits. PDS behaves aggressive compared to AFX. Thus, a precise delineation, although challenging in some instances, is relevant.MethodsWe examined the value of DNA-methylation profiling and copy number analysis for separating these tumors. DNA-methylation data were generated from 17 AFX and 15 PDS using the Illumina EPIC array. These were compared with DNA-methylation data generated from 196 tumors encompassing potential histologic mimics like cutaneous squamous carcinomas (cSCC; n = 19), basal cell carcinomas (n = 10), melanoma metastases originating from the skin (n = 11), leiomyosarcomas (n = 11), angiosarcomas of the skin and soft tissue (n = 11), malignant peripheral nerve sheath tumors (n = 19), dermatofibrosarcomas protuberans (n = 13), extraskeletal myxoid chondrosarcomas (n = 9), myxoid liposarcomas (n = 14), schwannomas (n = 10), neurofibromas (n = 21), alveolar (n = 19) and embryonal (n = 17) rhabdomyosarcomas as well as undifferentiated pleomorphic sarcomas (n = 12).ResultsDNA-methylation profiling did not separate AFX from PDS. The DNA-methylation profiles of the other cases, however, were distinct from AFX/PDS. They reliably assigned to subtype-specific DNA-methylation clusters, although overlap occurred between some AFX/PDS and cSCC. Copy number profiling revealed alterations in a similar frequency and distribution between AFX and PDS. They involved losses of 9p (22/32) and 13q (25/32). Gains frequently involved 8q (8/32). Notably, a homozygous deletion of CDKN2A was more frequent in PDS (6/15) than in AFX (2/17), whereas amplifications were non-recurrent and overall rare (5/32).ConclusionsOur findings support the concept that AFX and PDS belong to a common tumor spectrum. We could demonstrate the diagnostic value of DNA-methylation profiling to delineating AFX/PDS from potential mimics. However, the assessment of certain histologic features remains crucial for separating PDS from AFX.

Subcutaneous undifferentiated pleomorphic sarcoma is more aggressive than pleomorphic dermal sarcoma: Prognosis from a Danish nationwide registry-based cohort.

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare cutaneous malignancies that predominantly affect older individuals, often arising in sun-exposed areas. This study represents the first UK-based outcome analysis of AFX and PDS from a major tertiary hospital, reviewing all cases diagnosed between January 2014 and 20 August 2019. A retrospective cohort study identified 94 patients initially diagnosed with AFX. Of these, 15 cases were reclassified as PDS, leaving 79 confirmed AFX cases. Separately, 42 patients were identified with PDS. Patient demographics, lesion characteristics, histopathological features, treatment modalities and follow-up outcomes were analysed. AFX predominantly affected men (n = 74, 94%), and the patients had a median age of 79 years. Six patients were immunosuppressed. Most lesions (n = 76, 96%) were on the head and neck. Histopathological findings showed dermal involvement in 53 cases, subcutaneous extension in 13, and fascia involvement in one. Mitosis was present in 38 cases, necrosis in two, and perineural invasion (PNI) in one. Lymphovascular invasion was identified in three cases. Excision was incomplete in three cases, and five had narrow margins. PDS was more frequent in men (n = 36, 86%) and the median age was 81 years. Eight patients were immunosuppressed or had related conditions. Most lesions (n = 40, 95%) were on the head and neck. Tumours extended into the subcutis in 26 cases, fascia in 10, and bone in four. Mitosis was present in 36 cases, necrosis in six, PNI in nine (one suspected) and lymphovascular invasion in one. Excision was incomplete in three cases, and 15 had narrow margins. In AFX, no deaths, recurrences or metastases were observed. Follow-up varied: 35 patients were monitored for 1–2 years, 17 for &amp;gt; 2 years, and nine for &amp;lt; one year. Five patients had no follow-up (1 due to death). In PDS, five deaths were attributed to the condition, with one contributory case. Imaging at diagnosis was performed in 27 patients. Local recurrence occurred in nine cases, distant recurrence in seven (one likely but unproven) and lymph node metastasis in three. Some patients were followed for up to 10 years, while others had follow-up cut short due to death or ill health. In conclusion, AFX and PDS primarily affect older men, with lesions commonly occurring on the head and neck. AFX exhibited a favourable prognosis, with no recurrences or disease-related mortality, whereas PDS demonstrated a more aggressive clinical course, with a higher recurrence rate, more distant metastases and greater disease-related mortality. This study is the first UK-based outcome analysis of AFX and PDS from a large tertiary hospital.

Description Pleomorphic dermal sarcoma (PDS) can clinically and histopathologically mimic atypical fibroxanthoma (AFX). However, it has a more aggressive clinical course with a higher recurrence rate and metastatic potential. This case presentation aims to report a rapidly-growing, exophytic, 4 cm tumor following a non-diagnostic shave biopsy 2 months prior and to highlight distinctive features between PDS and AFX needed to make the correct diagnosis. Like AFX, PDS occurs on the sun-damaged skin of the elderly, usually on the head and neck. Also, like AFX, PDS histopathologically consists of sheets or fascicles of epithelioid and/or spindle-shaped cells, often with multinucleation, pleomorphism, and numerous mitotic figures. Immunohistochemistry cannot distinguish PDS from AFX but is used to exclude other malignancies. PDS can be distinguished from AFX by size (PDS is usually >2.0 cm) and by the presence of more aggressive histopathologic features, such as subcutaneous involvement, perineural and/or lymphovascular invasion, and necrosis. PDS is a rare entity not well documented in the literature with confusing, misleading, and changing nomenclature. PDS is a diagnosis of exclusion made after complete excision of the tumor with the aid of histopathology and immunohistochemistry.

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.

Metastatic pleomorphic dermal sarcoma to small bowel – A case report

Pleomorphic dermal sarcoma is a rare neoplasm of mesenchymal origin that most commonly affects the head. We describe the presentation of a 61-year-old man with a 10-week history of an exophytic lesion affecting the occipital scalp, demonstrating rapid growth. The final histopathology revealed a completely excised 9cm pleomorphic dermal sarcoma (pT2aN0M0, Stage 3), one of the largest such lesions reported in the literature to date. This patient's management involved a wide local subperiosteal excision onto the cranium, with a reconstruction with an Integra dermal regeneration template (Integra LifeSciences, Princeton, NJ, USA) and healing with secondary intention. This was mainly due to poorly defined clinical margins on primary excision, the potential for further excision of involved margins (later confirmed as not needed) and the patient's comorbidities, making a return to theatre for definitive reconstruction undesirable.

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.