Spindle Cell Atypical Fibroxanthoma

Abstract

Atypical fibroxanthoma (AFX) is a low-grade, dermal, mesenchymal neoplasm, which lacks a specific lineage of differentiation. The classical histologic appearance of AFX is that of a pleomorphic and spindle cell neoplasm with marked nuclear pleomorphism, mitotic figures, and often prominent storiform pattern that superficially resembles a pleomorphic high-grade sarcoma ("malignant fibrous histiocytoma"). Many histologic variants have been described. We have reviewed 15 cases of AFX characterized by a pure spindle cell morphology that could be easily mistaken for other spindle cell dermal neoplasms. All of our cases were stained with CD68, CD163, CD10, S-100p, p63, wide-spectrum keratin, CD31, CD34, smooth muscle actin (SMA), desmin, calponin, and h-caldesmon. All 15 cases showed an immunoprofile consistent with AFX. In 9 cases, SMA was also strongly expressed; this finding, coupled with the malignant spindle cell histomorphology, can lead to an erroneous diagnosis of cutaneous leiomyosarcoma with potential clinical consequences. Awareness of this pattern of immunoreactivity in this unusual variant of AFX is of importance for avoiding diagnostic misinterpretation. This study intends to characterize the nature and frequency of SMA immunoreactivity in AFX and to discuss the potential diagnostic pitfalls of immunohistochemical markers in distinguishing this entity from other malignant spindle cell neoplasms.

Immunohistochemical Characteristics of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma: A Systematic Review and Meta-Analysis

“…After exclusion of immunomarkers that were reported by only one study, a total of 45 studies reporting on 36 immunomarkers in 1516 tumors were included. 1,7,9–12,14,18–55 A total of 1160 AFX tumors and 356 PDS tumors were analyzed. Thirty-four studies investigated markers from AFX tumors, 5 from PDS tumors, and 6 from both.…”

“…Furthermore, AFX and PDS share histopathological similarities with other spindle cell neoplasms, such as spindle cell SCC, spindle cell melanoma, cutaneous leiomyosarcoma (LMS), and cutaneous angiosarcoma (AS), which makes immunohistochemistry a key supplemental tool in the diagnosis of AFX and PDS. [7][8][9][10][11][12][13] During the recent decades, the increasing use of immunohistochemistry has led to the proposal of a range of immunomarkers to increase the accuracy of diagnosing AFX and PDS. 4,11,14,15 The purpose of this meta-analysis was to compile studies on immunomarkers that have been used on AFX and PDS in the literature and to analyze the markers' positive rates with meta-analytical methods.…”

“…Furthermore, AFX and PDS share histopathological similarities with other spindle cell neoplasms, such as spindle cell SCC, spindle cell melanoma, cutaneous leiomyosarcoma (LMS), and cutaneous angiosarcoma (AS), which makes immunohistochemistry a key supplemental tool in the diagnosis of AFX and PDS. 7–13…”

Pleomorphic Dermal Sarcoma With Metastasis to the Lung: A Case Report

“…However, currently, there are no reliable discriminatory immunomarkers that distinguish AFX from PDS. [14][15][16] PDS/AFX is an undifferentiated neoplasm of uncertain lineage characterized by immunohistochemical positivity for vimentin, CD10, and CD68 and negative for cytokeratins, p63, CD34, and melanoma markers (such as Melan A, S100 protein, and HMB45). CD10 negativity should suggest that the possibility of an alternative diagnosis.…”

Case of Pleomorphic Dermal Sarcoma of the Eyelid Treated with Micrographic Surgery and Secondary Intention Healing

“…PDS can be distinguished from myofibroblastic and smooth muscle lesions, such as leiomyosarcoma or pleomorphic rhabdomyosarcoma, by the absence of myofibroblastic markers including desmin, calponin, and h-caldesmon 11 12 , and smooth muscle histopathological features 13 . Myxofibrosarcoma may resemble the areas of myxoid differentiation in PDS, and stain with vimentin and only rarely focally for actin 14 .…”