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Spindle cell squamous cell carcinoma: This nodular tumor is centered within dermis and shows invasion of superficial subcutaneous adipose tissue (a). It is composed of intersecting fascicles of pleomorphic spindle cells (b) Higher magnification demonstrating nuclear pleomorphism and an atypical mitotic figure (c). The tumor extends to the overlying epidermis (d)
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This manuscript provides an overview of pleomorphic spindle cell tumors presenting on sun-damaged skin of the elderly and includes discussions of atypical fibroxanthoma, pleomorphic dermal sarcoma, spindle cell and metaplastic squamous cell carcinoma, spindle cell and dedifferentiated melanoma and poorly differentiated cutaneous angiosarcoma. These...
Citations
... 82 To that end, PDS should not be confused with deep-seated UPS of the extremities and trunk, which we have shown to be rich in COSMIC1 but poor in the UV signature. 27,82 Nevertheless, cutaneous pleomorphic spindle cell tumors, 84 such as PDS, are important differential diagnoses when considering the diagnosis of UM. Unlike melanoma, most PDS lack hotspot MAPK alterations and bear recurrent NOTCH1/2 and FAT1 inactivation mutations. ...
The distinction between undifferentiated melanoma (UM) or dedifferentiated melanoma (DM) from undifferentiated or unclassifiable sarcoma can be difficult and requires careful correlation of clinical, pathologic, and genomic findings. In this study, we examined the utility of mutational signatures to identify patients with UM/DM with particular attention as to whether this distinction matters for treatment since the survival of patients with metastatic melanoma has dramatically improved with immunologic therapy, while durable responses are less frequent in sarcomas. We identified 19 cases of UM/DM that were initially reported as unclassified or undifferentiated malignant neoplasm or sarcoma and submitted for targeted next-generation sequencing analysis (NGS). These cases were confirmed as UM/DM by virtue of harboring melanoma driver mutations, UV signature, and high tumor mutation burden (TMB). One case of DM showed melanoma in situ. Meanwhile, eighteen cases represented metastatic UM/DM. Eleven patients had a prior history of melanoma. Thirteen of nineteen (68%) of the tumors were immunohistochemically completely negative for four melanocytic markers (S100, SOX10, HMB45, and MELAN-A). All cases harbored a dominant UV signature. Frequent driver mutations involved BRAF (26%), NRAS (32%), and NF1 (42%). In contrast, the control cohort of undifferentiated pleomorphic sarcomas (UPS) of deep soft tissue exhibited a dominant aging signature in 46.6% (7/15) without evidence of UV signature. The median tumor mutation burden for DM/UM vs. undifferentiated pleomorphic sarcoma (UPS) was 31.5 vs. 7.0 muts/Mb (P < 0.001). A favorable response to immune checkpoint inhibitor (ICI) therapy was observed in 66.6% (12/18) of patients with UM/DM. Eight patients exhibited complete response and were alive with no evidence of disease at the last follow-up (median: 45.5 mo). Our findings support the usefulness of UV signature in discriminating DM/UM vs. UPS. Furthermore, we present evidence suggesting that patients with DM/UM and UV signature can benefit from ICI.
... Therefore, histological examination, in particular immunohistochemistry, plays an important role in finding the right diagnosis. Nevertheless, specific markers for AFX/PDS are still lacking [2,10]. In the last years, there has been an increased interest in AFX, with new insights concerning clinical, pathogenetical, and histological features of AFX [5,[9][10][11][12]. ...
... Nevertheless, specific markers for AFX/PDS are still lacking [2,10]. In the last years, there has been an increased interest in AFX, with new insights concerning clinical, pathogenetical, and histological features of AFX [5,[9][10][11][12]. First described by Helwig in 1963, AFX is a rare tumor entity with an estimated prevalence of 0.24 % [13]. ...
... AFX usually presents as erythematous or skin-colored nodules with ulceration in approximately 50 % of cases, with a diameter of up to several centimeters [1,16]. AFX predominantly appears on sun-exposed skin, especially the head region followed by neck and limbs [9,10,14,16,17]. The main risk factor for AFX development is the UV-induced mutation of p53 [5,25]. ...
Hintergrund und ziele:
In den letzten Jahren konnten umfassende Erkenntnisse über die Pathogenese, Diagnostik und Behandlung von kutanen Sarkomen, insbesondere des atypischen Fibroxanthoms (AFX) und pleomorphen dermalen Sarkoms (PDS) gesammelt werden. Beide Entitäten zeigten innerhalb der letzten Dekade steigende Inzidenzraten. Die vorliegende Studie diente der Untersuchung, welchen Einfluss die neuen Erkenntnisse auf die Fallzahlen von AFX/PDS im Vergleich zu anderen Sarkom-Entitäten haben.
Patienten und methodik:
Diese retrospektive Studie wurde an vier deutschen Hauttumorzentren durchgeführt und alle von zertifizierten Dermatopathologen bestätigten histopathologischen Befunde von kutanen Sarkomen (AFX, PDS, Dermatofibrosarcoma protuberans, kutanes Leiomyosarkom, Angiosarkom und Kaposi-Sarkom) in einem Zeitraum von sieben Jahren (2013-2019) evaluiert. Zusätzlich wurde der Einsatz von immunhistochemischen Markern als diagnostische Hilfe (Panzytokeratin, S100, Desmin, CD34, CD10, Prokollagen-1, CD99, CD14 und CD68) erfasst.
Ergebnisse:
Insgesamt konnten 255 kutane Sarkome in die vorliegende Studie eingeschlossen werden. Die Zahl der kutanen Sarkome nahm kontinuierlich von 2013 bis 2019 zu (von 16 auf 52 Fälle im Jahr). Die Diagnose eines AFX/PDS konnte in 2019 4,6-mal häufiger als in 2013 gestellt werden. Das AFX stellte mit 49,3 % aller kutanen Sarkome den häufigsten Sarkom-Subtypen dar. Zusätzlich war der Anstieg von AFX/PDS mit dem Einsatz von Immunhistochemie assoziiert. Der Einsatz von spezifischen Immunhistochemischen Markern stieg von 57,1 % im Jahr 2013 auf 100 % in 2019.
Schlussfolgerungen:
Diese retrospektive Studie von vier deutschen Hauttumorzentren demonstriert eine substanzielle Zunahme von AFX/PDS, wahrscheinlich infolge kürzlich etablierter beziehungsweise verbesserter diagnostischer und terminologischer Standards. Dieser Anstieg ist vermutlich mit dem vermehrten Einsatz von bestimmten immunhistochemischen Markern assoziiert. AFX/PDS treten wahrscheinlich häufiger auf als bisher vermutet und repräsentieren möglicherweise den häufigsten kutanen Sarkom-Subtyp.
... Therefore, histological examination, in particular immunohistochemistry, plays an important role in finding the right diagnosis. Nevertheless, specific markers for AFX/PDS are still lacking [2,10]. In the last years, there has been an increased interest in AFX, with new insights concerning clinical, pathogenetical, and histological features of AFX [5,[9][10][11][12]. ...
... Nevertheless, specific markers for AFX/PDS are still lacking [2,10]. In the last years, there has been an increased interest in AFX, with new insights concerning clinical, pathogenetical, and histological features of AFX [5,[9][10][11][12]. First described by Helwig in 1963, AFX is a rare tumor entity with an estimated prevalence of 0.24 % [13]. ...
... AFX usually presents as erythematous or skin-colored nodules with ulceration in approximately 50 % of cases, with a diameter of up to several centimeters [1,16]. AFX predominantly appears on sun-exposed skin, especially the head region followed by neck and limbs [9,10,14,16,17]. The main risk factor for AFX development is the UV-induced mutation of p53 [5,25]. ...
Background and objectives:
In recent years, considerable insight has been gained into the pathogenesis, diagnosis and treatment of cutaneous sarcomas, including atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS). Both entities have shown increasing incidence rates in the last decade. This study was initiated to evaluate how these new insights impact the number of diagnoses of AFX/PDS compared to other cutaneous sarcoma entities.
Patients and methods:
In a retrospective study of four German skin cancer centers, all histopathological reports of cutaneous sarcomas (AFX, PDS, dermatofibrosarcoma protuberans, cutaneous leiomyosarcoma, angiosarcoma, and Kaposi sarcoma) confirmed by board-certified dermatopathologists were analyzed during a time-period of seven years (2013-2019). Additionally, utilization of immunohistochemical markers (including pan-cytokeratin, S100, desmin, CD34, CD10, procollagen-1, CD99, CD14, and CD68) as an adjunct to diagnose AFX/PDS was recorded.
Results:
Overall, 255 cutaneous sarcomas were included in the present study. The diagnosis of a cutaneous sarcoma has consequently risen from 2013 to 2019 (from 16 to 52 annual cases). The results of AFX/PDS revealed 4.6 times more diagnoses in 2019 than in 2013. Atypical fibroxanthoma represented the most common subtype, displaying 49.3 % of all diagnosed cutaneous sarcomas. Additionally, the increase of AFX/PDS was linked to the use of immunohistochemistry, with specific immunohistochemical markers used in 57.1 % of cases in 2013 compared to 100 % in 2019.
Conclusions:
This retrospective study of four German skin cancer centers demonstrates a substantial rise of AFX/PDS, possibly due to recently established diagnostic and terminology standards. This rise is probably linked to increased utilization of specific immunohistochemical markers. Atypical fibroxanthoma/PDS may be more common than previously thought and seems to represent the most frequent cutaneous sarcoma subtype.
... Pleomorphic dermal sarcoma is poorly marginated, deeply invasive, rapid growing lesion. Frequent mitosis, tumor necrosis and pleomorphism should present [13]. Lymph-vascular invasion exists in some cases Keratins, S100, Desmin, CD34, are negative [13]. ...
... Frequent mitosis, tumor necrosis and pleomorphism should present [13]. Lymph-vascular invasion exists in some cases Keratins, S100, Desmin, CD34, are negative [13]. Sarcomatoid melanoma has a sarcomatous component which further make it fair easily identified from spindle cell melanoma and desmoplastic melanoma. ...
... Pleomorphic dermal sarcoma (PDS) and atypical fibroxanthoma (AFX) are uncommon mesenchymal neoplasms that mainly present in sun-damaged regions of elderly patients and share histopathologic and immunohistochemical (IHC) features [1,2]. PDS displays more aggressive clinical behavior than AFX and has a higher rate of recurrences, with some studies reporting an average of 20-30% rates of local recurrence and 10-20% rates of distant recurrences [2][3][4]. ...
Pleomorphic dermal sarcoma is an uncommon mesenchymal neoplasm that shares clinical, immunohistochemical, and histopathologic features with atypical fibroxanthoma but with additional aggressive histopathologic features. This tumor is not well documented in the literature, its clinical features are poorly characterized, and diagnosis is still by exclusion. To better understand this disease, we performed a comprehensive systematic review and included clinical, immunohistochemical, and histopathologic data of five patients (median age: 81) from our own institution. Elderly men are typically affected more than women and the tumor presents as an exophytic growth on sun-damaged regions of the head and scalp, although our cohort had three men and two women. Histologically, the tumors display brisk mitotic activity with asymmetrical lesions; pleomorphic spindle cells; and large, multinucleated giant cells with vacuolated cytoplasm arranged in fascicular patterns. Eighty percent of patients displayed deep tissue invasion and 40% displayed perineural invasion. Immunohistochemical stains for CD10 and CD68 were positive in 60%, and all patients tested were negative for S-100, PanCK, desmin, MART-1, SOX-10 CD-34, P40, SMA, and CK-5/6. Recurrence and further clinical data were not collected due to loss of follow-up. Although there are no standardized treatment guidelines, wide local excision is recommended. The consensus is that pleomorphic dermal sarcoma has a more aggressive disease course than atypical fibroxanthoma with poorer outcomes. Our study creates the first comprehensive treatment recommendations in the literature for better risk stratification, prognoses, and outcomes.
... AFX and PDS are genetically related, potentially representing two ends of a common tumor spectrum [134]. PDS can be distinguished from AFX by subcutaneous invasion, tumor necrosis, and perineural or lymphovascular invasion [135,136]. DFSP is a superficial, low grade, locally aggressive neoplasm characterized by monomorphic spindle cells arranged in storiform pattern and honeycomb pattern of subcutaneous infiltration [137]. DFSP can show broad morphological variation, including myxoid change, granular cell change, myoid differentiation, pigmented dendritic cells, giant cell fibroblastoma-like morphology, and fibrosarcomatous transformation [138,139]. ...
Epithelioid cells are rounded or polygonal cells with abundant eosinophilic or clear cytoplasm and ovoid to round nuclei, superficially resembling epithelial cells. Cutaneous mesenchymal neoplasms composed predominantly or exclusively of epithelioid cells are relatively uncommon and can cause considerable diagnostic difficulties due to overlapping histologic features among heterogeneous groups of tumors. Familiarity with practical diagnostic approaches and recognition of key histopathologic features are important for correct diagnosis and management. This review summarizes the histologic features of epithelioid cutaneous mesenchymal neoplasms and discusses their differential diagnoses from malignant melanomas and carcinomas.
A 78-year-old man underwent ⁶⁸ Ga–prostate-specific membrane antigen-11 (PSMA-11) PET/CT for biochemical recurrence of prostate adenocarcinoma following a simple prostatectomy. The scan showed PSMA-avid local recurrence within the prostatectomy bed and a suspicious right internal iliac nodal metastasis. In addition, there was a mildly avid subcutaneous lesion in the right flank, which revealed high-grade spindle cell sarcoma at histopathology. This case represents a potential pitfall for PSMA-11 PET imaging. The presentation of mildly avid, atypical soft tissue lesions should warrant a biopsy to allow for proper diagnosis and treatment management.
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 programs 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 2002-2022 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 three 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 four years. Patients with PDS should be followed with clinical visits and PET/CT twice a year for the first three years and once a year for a minimum of one year.
Atypical fibroxanthoma (AFX) is an uncommon, primary dermal neoplasm of uncertain histogenesis, typically originating in the sun-damage skin of the head and neck of the elderly. Since first description in 1958, ∼3000 cases have been reported in the literature. However, the disease is underreported as the neoplasm is considered a standard diagnosis in the last decades. On the other hand, many earlier reports likely have included non-AFX mimics or aggressive pleomorphic dermal sarcomas. In contrast to its alarming high-grade histology, AFX behaves indolently with rare recurrences/ metastatic rate of <2%. The overall 10- and 20-year disease-specific survival rates are ∼ 100% and 98%, respectively. Histologically, AFX displays undifferentiated pleomorphic spindle cell morphology akin to undifferentiated pleomorphic sarcoma (UPS), a feature that was the basis of the abandoned historical terminology "MFH of skin". However, in contrast to other undifferentiated sarcomatoid neoplasms, AFX is notorious for its highly variable histology with a plethora of patterns, underlining a wide differential diagnosis. Notably, spindle cell, keloid-like, pleomorphic, epithelioid, rhabdoid, clear cell, foamy cell, granular cell, bizarre cell, pseudoangiomatous, inflammatory, osteoclast-rich, and many others have been recognized with varying frequencies. Immunohistochemically, AFX is characterized by nonspecific profile with block-type expression of CD10 and aberrant p53 pattern and lack of pankeratin and other lineage-specific epithelial, mesenchymal, melanocytic and hematolymphoid markers. Sarcomatoid melanoma, spindle cell carcinoma and cutaneous anaplastic large cell lymphoma are major considerations. Distinction of AFX from pleomorphic dermal sarcoma (PDS) is arbitrary and is based on presence of ≥ 1 of four unfavorable histological features: more than minimal subcutaneous involvement, coagulative necrosis, lymphovascular invasion and perineurial invasion.
