Atypical fibroxanthoma with prominent sclerosis

BACKGROUND: Malignant cutaneous spindle cell lesions with marked sclerosis are uncommon. Only a few cases of cutaneous leiomyosarcoma and dermatofibrosarcoma protuberans with sclerosis have been published. METHODS: We report a case of atypical fibroxanthoma (AFX) with prominent sclerosis and hyalinization occurring on the scalp of an 81-year-old male. RESULTS: Histopathologic examination revealed an exophytic, well-delineated, focally ulcerated tumor arising in sun-damaged skin. The lesion was composed of atypical spindle cells arranged in a fascicled and vaguely storiform pattern. Occasional multinucleated giant cells were present. The tumor cells were strongly positive for CD99 (O13), vimentin, and smooth muscle actin, and focally positive for CD68. There was striking sclerosis with hyalinization throughout the lesion. CONCLUSIONS: Rarely, AFX may exhibit marked sclerosis with areas of complete replacement of tumor by hyalinized collagen. In a small biopsy, such hyalinization may be a diagnostic pitfall leading to an erroneous diagnosis.     

Atypical fibroxanthoma with lymphomatoid reaction

Background: Atypical fibroxanthoma (AFX) represents an uncommon skin tumor typically occurring on sun‐damaged skin of the elderly. Histopathologic variants include spindled, clear cell, osteoid, osteoclastic, chondroid, pigmented, granular cell and myxoid lesions. To date, an atypical lymphoid infiltrate, including CD30‐positive large cells mimicking lymphomatoid papulosis, has not been described in association with AFX. Methods: The clinical and histopathological characteristics of two AFX cases inciting an atypical lymphoid infiltrate, along with immunohistochemical profiles and T‐cell receptor gamma (TCRγ) gene rearrangement results, were reviewed. Results: Lesions in both cases occurred as solitary nodules in elderly patients. Microscopically, both lesions showed a cellular proliferation composed of pleomorphic spindle cells, associated with a prominent intralesional atypical lymphoid infiltrate. The spindle cells expressed CD10 but lacked the expression of S‐100, cytokeratins and muscle markers, thereby confirming the diagnosis of AFX. CD30 highlighted a significant subset of large mononuclear cells in the lymphoid infiltrate of one case. TCRγ gene rearrangement analyses were negative for both cases. Conclusion: An atypical lymphoid infiltrate, including the one resembling lymphomatoid papulosis, associated with AFX has not been previously described. It is important to recognize the reactive nature of the infiltrate to avoid a misdiagnosis of lymphoma. Zheng R, Ma L, Bichakjian CK, Lowe L, Fullen DR. Atypical fibroxanthoma with lymphomatoid reaction.     

Atypical fibroxanthoma with dermal amyloid deposit

Atypical fibroxanthoma (AFX) has been associated with several secondary changes, such as keloidal areas, myxoid or chondroid changes, osteoclast-like giant cells, sclerosis, fibrosis, pigmentation, hyalinization, or hemorrhagic areas. We report a case of an AFX 4 cm in diameter on the forehead of a 77-year-old male patient. There were dermal amyloid deposits intermingled with the tumor fascicles on the periphery of the lesion. A moderate inflammatory chronic lymphoplasmacytic infiltrate was found in the periphery of the tumor. The amyloid deposits were positive with Congo red staining (but negative after permanganate-treatment). The deposit was also immunostained with antibodies against CKs (AE1/AE3 and CK5/6). It did not stain with anti-amyloid A, or with antibodies against either kappa light or lambda light chains. Therefore the amyloid deposit was keratinic in nature.     

Granular cell atypical fibroxanthoma: report of two cases

Two cases of an uncommon histopathological variant of atypical fibroxanthoma (AFX) are described. Even though both lesions presented as clinically conventional atypical fibroxanthoma, histopathology disclosed a neoplasm composed of cells with granular change that was negative for S100 staining, and showed prominent pleomorphism, severe nuclear atypia, and a high mitotic index. Degenerative change may explain the granular phenotype in these two cases of AFX. The differential diagnosis with primitive nonneural granular cell tumor is discussed.     

Keloidal atypical fibroxanthoma: a case series

Background:  Keloidal atypical fibroxanthoma (AFX) is a rare variant of AFX with thick bands of hyalinized collagen. The identification of keloidal collagen associated with fibrohistiocytic cells may erroneously lead to the diagnosis of keloidal dermatofibroma. Although AFX is a pleomorphic cutaneous tumor typically associated with a good prognosis, occasional reports of metastatic AFX highlight the importance of accurate identification.
Methods:  A total of nine cases of an unusual variant of AFX with keloidal tumoral sclerosis were collected and examined. The cases were stained with antibodies directed against S100, cytokeratin, CD68 and CD31.
Results:  Histopathological examination revealed pleomorphic cells trapped within hyalinized keloidal collagen bands. In several cases, the keloidal collagen also formed ring-shaped structures surrounding CD31-positive vascular structures. Pleomorphic cells were negative for S100 protein and keratin, but consistently labeled with antibodies directed against CD68.
Conclusions:  The diagnosis of keloidal AFX requires the exclusion of other malignant and benign lesions with keloidal or sclerotic collagen. Awareness of the rare variant of keloidal AFX may avoid a diagnostic pitfall leading to an erroneous diagnosis, particularly in small biopsies. The finding of sclerotic collagen preferentially deposited around vessels is an interesting and poorly understood phenomenon.     

Clear cell atypical fibroxanthoma: a case report and review of the literature

Atypical fibroxanthoma (AFX) is a group of cutaneous tumors characterized by a population of fusiform, epithelioid and pleomorphic cells. Clinically, AFX is commonly found on the head and neck of older adults as a solitary ulcerated nodule. Clear cell atypical fibroxanthoma is a very rare variant of AFX, with only 13 cases reported to date. The differential diagnoses often include dermal neoplasms composed of clear cells, such as squamous cell carcinoma, basal cell carcinoma, metastatic renal cell carcinoma and balloon cell malignant melanoma. These diagnoses can be ruled out by the typical immunohistochemical profile of clear cell AFX, which is negative for specific epithelial and melanocytic markers. Herein, we describe a rare and unusual case of clear cell AFX arising on the ear of a relatively young adult patient. Histologically, the dermis was completely replaced by an atypical population of vacuolated cells with numerous atypical mitoses. Immunohistochemical stains were negative forpancytokeratin, CK5/6, CK7, and p63 S100 and Melan‐A stains. CD10 and CD68 stains were positive, making the findings consistent with the diagnosis of clear cell atypical fibroxanthoma.     

A rare low-grade malignant scalp tumor. Atypical fibroxanthoma

A 79-year-old patient presented with an asymptomatic scalp tumor which had grown over the past 9 months. Based on clinical, histological and immunohistochemical staining, we made the diagnosis of an atypical fibroxanthoma (AFX). AFX is a rare tumor, but important in the differential diagnosis of other scalp tumors. The routine histological staining allows one to identify a malignant fibrous histiocytoma, while a spindle-cell malignant melanoma can be excluded with immunohistochemical staining. An anaplastic squamous cell carcinoma cannot always be separated with completed certainty from atypical fibroxanthoma. AFX is a low-grade malignant tumor and most cases behave in a benign fashion. After complete excision, we recommend follow-up for a number of years because of the possibility of local recurrence.     

Myofibroblastic differentiation in atypical fibroxanthomas occurring on sun-exposed skin and in a burn scar: an ultrastructural and immunohistochemical study

Herein, we report the investigation of two cases of atypical fibroxanthoma (AFX). One AFX developed within actinically damaged skin, as is typical, while the other developed within a burn scar within non-sun-exposed skin. The two tumors showed almost identical histopathological, immunohistochemical and ultrastructural features. The tumors were composed of pleomorphic spindled, epithelioid, multinucleated and bizarre cells with enlarged atypical nuclei. Most tumor cells expressed vimentin and about 50% expressed CD10. Some tumor cells also expressed α-smooth muscle actin and CD68. However, there was no expression of cytokeratins, p63, S-100 protein, melan-A, HMB 45, desmin, epithelial membrane antigen or CD34. Ultrastructurally, the tumor cells contained myofilaments with dense patches but lacked plasmalemmal caveolae and basal lamina. The most prominent finding was the identification of fibronexus junctions. In addition, there were tumor cells containing numerous lysosomal granules. In conclusion, we clearly showed myofibroblastic differentiation in AFX by electron microscopy. We report also a case of AFX directly developing within a burn scar in the absence of actinic damage.     

Atypical fibroxanthoma-like amelanotic malignant melanoma: A case report and literature review

Atypical fibroxanthoma (AFX)-like malignant melanoma is very rare. Here, we report a case of amelanotic AFX-like melanoma in a 72-year-old Taiwanese woman presenting with two separate, asymptomatic, enlarging erythematous nodules within a large hypopigmented patch on her left cheek. Histologically, both lesions showed cellular nodules in the reticular dermis separated from the overlying flattened epidermis by a zone of solar elastosis or fibrosis. The tumor consisted of sheets of atypical epithelioid cells arranged in a vague nesting pattern, as well as many atypical large or gigantic cells with one or more, large hyperchromatic, vesicular, or pleomorphic nuclei with prominent nucleoli, and moderate-to-abundant eosinophilic or foamy cytoplasm. Focal intraepidermal proliferation of atypical melanocytes with a pagetoid pattern was found only in the periphery of the main tumor. The tumor cells were moderately to strongly positive for S-100, Melan-A, and HMB-45. The pleomorphic giant cells were focally CD68-positive but CD163-negative. The patient underwent tumor excision followed by radiotherapy due to the narrow surgical margins. A sentinel lymph node biopsy revealed no metastasis of the melanoma. This case illustrates the importance of scrutinizing any subtle proliferation of atypical melanocytes in the epidermis in an AFX-like tumor in order to avoid misdiagnosis.     

CD163 is not a sensitive marker for identification of atypical fibroxanthoma

The histopathological features of atypical fibroxanthoma (AFX) overlap with those of poorly differentiated carcinoma, melanoma and leiomyosarcoma in the skin. As there are no specific stains to identify AFX, the diagnosis is essentially one of exclusion and requires completion of a panel of immunostains. Recently, it has been suggested that the macrophage/monocyte-specific marker CD163 is of value in identifying AFX. To investigate this claim, 57 AFX were stained for CD163. Only 21 of 57 (37%) of AFX stained positively, and intratumoral macrophages confounded interpretation of the stain at times. In four cases, it was not possible to definitively interpret the tumor staining reaction because of this effect. While a lack of stainable CD163 antigenicity may indicate that AFX is not of histiocytic lineage, it is conceivable that expression of the antigen has been lost for some reason in cells that are in fact of macrophage lineage. In summary, CD163 only stains a minority of AFX and staining results can be difficult to interpret. CD163 is therefore of very limited value in the diagnosis of AFX. Beer TW. CD163 is not a sensitive marker for identification of atypical fibroxanthoma.     

Clear cell atypical fibroxanthoma - report of a case with review of the literature

Clear cell atypical fibroxanthoma (CCAFX) is a rare variant of atypical fibroxanthoma (AFX), a pleomorphic dermal tumour associated with a good prognosis. A 67-year-old man presented with a rapidly growing nodule on the ear, which had appeared over a 2-week period. Sections showed an ulcerated nodule composed of pleomorphic spindled and polygonal cells with clear cytoplasm, invested by a delicate vascular stroma, reminiscent of clear cell renal cell carcinoma. Numerous mitotic figures were seen. The tumour cells stained with vimentin, CD68 and CD99 and were cytokeratin-negative. The immunohistochemical and ultrastructural features supported a diagnosis of CCAFX. The diagnosis of CCAFX requires the exclusion of other pleomorphic clear cell tumours that can occur in the skin by using a combination of morphology, immunohistochemistry and electronmicroscopy. Murali R, Palfreeman S. Clear cell atypical fibroxanthoma - report of a case with review of the literature.     

Atypical fibroxanthoma with perineural or intraneural invasion: report of two cases

We report two cases of atypical fibroxanthoma (AFX) that both had the previously unreported feature of neural invasion (one perineural and the other intraneural). AFXs recur in approximately 10% of cases but only rarely metastasize. Features associated with recurrence are inadequate excision and invasion into fat. Features associated with metastasis include recurrence, vascular invasion, deep tissue invasion, and tumor necrosis. Both of these tumors invaded deeply into subcutaneous fat and reached the deep fascia. Some authors would regard such cases as malignant fibrous histiocytoma (MFH) because of such deep extension; however, the concept of AFX as a superficial variant of MFH is outmoded--AFX is a distinct clinicopathologic entity with established clinical, histological, and immunohistochemical features.     

ATYPICAL FIBROXANTHOMA OF THE SKIN A HISTOLOGICAL AND ELECTRON MICROSCOPIC STUDY

A histological and electron microscopic case study of an atypical fibroxanthoma (AFX) of the skin was reported. The lesion developed on the left lower limb of a 23-year-old woman. Histologically, the lesion showed three zonal arrangements: spotty, small necrotic foci filled with erythrocytes in the central zone, pleomorphic and atypical cells in the intermediate zone; and interlacing collagenous bundles with storiform patterns in the peripheral zone. Tumor cells identified by electron microscopy were divided into undifferentiated mesenchymal, fibroblast-like, histiocyte-like and xanthoma cells. This suggested, histogenetically, that tumor cells of AFX of the skin may be fibrohistiocytic in nature. Furthermore, lipid droplets in xanthoma cells were classified into two types: smooth, oval or round shapes without a limiting membrane; irregular shapes with a limiting membrane.     

An unusual presentation of atypical fibroxanthoma

Atypical fibroxanthoma (AFX) is a rare cutaneous spindle-cell neoplasm. The tumor occurs most commonly in sun-damaged skin of the head and neck in elderly patients. A small subset of patients (approximately one in five cases) is middle-aged and presents with AFX of the trunk or extremities in areas without evidence of actinic damage. We report an unusual case of AFX of the lower leg in an 81-year-old woman with extensive actinic damage.     

Dermatoscopic features of cutaneous atypical fibroxanthoma: three cases

Atypical fibroxanthoma (AFX) is an uncommon, low‐grade, malignant, spindle‐cell tumour of fibrohistiocytic histogenesis, which can mimic other malignant skin tumours, such as basal and squamous cell carcinoma (CC), melanoma, and Merkel cell carcinoma (MCC). Three cases of AFX were examined by dermatoscopy, which revealed white areas and an atypical polymorphous vascular pattern characterized by the concurrence of different structures: linear, dotted, hairpin, arborescent and highly tortuous vessels, irregularly distributed over the surface. Seborrhoeic elements and photoageing may be accompanying features depending on the anatomical location of the AFX. AFX may be added to the list of slightly pigmented, reddish, malignant cutaneous tumours, such as SCC, MCC, amelanotic/hypomelanotic melanoma and eccrine porocarcinoma, which display prominent and chaotic dermatoscopic neoangiogenetic features in more advanced stages of proliferation.     

Metastasizing soft tissue tumor of light damaged skin: atypical fibroxanthoma or malignant fibrous histiocytoma?

A 86-year-old female patient presented with a ca. walnut-sized, centrally ulcerated preauricular tumor on the right side as well as a firm submandibular lymph node. Histology disclosed a soft-tissue tumor breaking into the lymph node consisting partly of fibroblast-like and partly of histiocyte-like cells. Clinical and histological criteria speak for both an atypical fibroxanthoma (AFX) as well as a malignant fibrous histiocytoma (MFH). A differentiation into two entities does not appear appropriate in our opinion. As the term "AFX" is classified as a benign tumor, "metastasizing AFX" (mAFX) should be considered a special form of MFH or be diagnosed as such, respectively.     

The role of CD10 in distinguishing atypical fibroxanthoma from sarcomatoid (spindle cell) squamous cell carcinoma

Background: The role of CD10 needs clarification in a broader immunohistochemical battery for distinguishing atypical fibroxanthoma (AFX) from spindle cell squamous cell carcinoma (sSCC). Methods: We retrospectively reviewed 23 cutaneous spindle cell tumors previously classified as AFX (n = 11) or as sSCC (n = 12). Each tumor was stained with CD10, S‐100, p63 and two or more cytokeratin stains. Defining AFX as a diagnosis of exclusion based on multiple negative cytokeratin stains and negative p63 staining, we reclassified four squamous cell carcinomas (SCCs) as AFX. CD10 staining was reviewed and graded in all tumors. Results: Fifteen tumors were classified as AFX. Strongly positive CD10 staining was observed in all 15 AFXs, as well as four (50%) of the eight SCCs. Expression of p63 was seen in six sSCCs (75%). Conclusions: CD10 is consistently expressed by AFX. However, CD10 is also often strongly expressed by sSCC. Positive staining with p63 favors a diagnosis of sSCC. An immunohistochemical battery useful for distinguishing AFX from sSCC may include CD10, p63 and two cytokeratin markers. However, CD10 alone should not be relied upon in the distinction of these entities. Wieland CN, Dyck R, Weenig RH, Comfere NI. The role of CD10 in distinguishing atypical fibroxanthoma from sarcomatoid (spindle cell) squamous cell carcinoma.     

Ultrastructure of Spindle Cell Squamous Carcinoma

A 63-year-old white male presented with a nine-month history of a nontender ulcerated lesion on his ear. Light microscopy demonstrated a moderately well circumscribed lesion in the dermis which abutted upon epidermis. There was no evidence of continuity between the tumor and overlying epithelium. The tumor was very cellular with an admixture of cells - spindle, polyhedral and bizarre giant cells. Mitotic figures were abundant and frequently abnormal. We interpreted this lesion to have the clinical and pathologic features of an atypical fibroxanthoma (AFX). Ultrastructure, however, showed abundant tonofilaments and desmosomes indicative of an epithelial origin and therefore most consistent with a spindle cell squamous carcinoma (SCSC). It is urged that, when possible, electron microscopy be performed on problematic cases diagnosed either as an AFX or spindle cell squamous carcinoma since it is the most valid basis on which a correct diagnosis can be made.     

Aneuploidy in atypical fibroxanthoma: DNA content quantification of 10 cases by image analysis

It has recently been reported that atypical fibroxanthoma (AFX) is a predominantly diploid lesion in contrast to malignant fibrous hystiocytoma (MFH) which is usually aneuploid. To test this hypothesis, DNA content quantification was undertaken on Feulgen-stained cytology and tissue section preparations from 10 cases of AFX by image analysis. The large-atypical cells which characterize AFX were aneuploid in each case. Smaller spindle-shaped cells found in this lesion were diploid. The results suggest that AFX is indistinguishable from MFH by DNA content estimation and highlight an advantage of image analysis over (low cytometry.     

Aberrant Melan-A expression in atypical fibroxanthoma and undifferentiated pleomorphic sarcoma of the skin

Background: Atypical fibroxanthoma (AFX) is a distinctive clinicopathologic entity presenting on sun‐damaged skin of the elderly. Its behavior is benign if strict diagnostic criteria are applied. Tumors showing invasion of deeper structures or perineural/lymphovascular invasion are best regarded as undifferentiated pleomorphic sarcoma of the skin. The diagnosis requires immunohistochemical studies to exclude melanoma, squamous cell carcinoma, angiosarcoma and leiomyosarcoma. Methods: Two AFX and one undifferentiated pleomorphic sarcoma showing aberrant expression of Melan‐A were identified. Clinical data were obtained and histopathological features, immunohistochemical profile and electron microscopy were assessed. Results: All tumors arose on sun‐damaged skin of elderly males. Two AFX showed pushing growth into superficial subcutis only. The undifferentiated pleomorphic sarcoma was characterized by infiltrative growth into galea as well as perineural invasion. Multifocal expression of Melan‐A and MART‐1 was largely limited to tumor giant cells in the absence of S100 or HMB‐45 labeling. No melanosomes or premelanosomes were identified by electron microscopy. Conclusions: Aberrant expression of Melan‐A and MART‐1 in AFX and undifferentiated pleomorphic sarcoma of the skin represents an important diagnostic pitfall with potential for misdiagnosis as melanoma. Melan‐A expression limited to tumor giant cells, in the absence of S‐100 positivity, is a helpful diagnostic feature. Thum C, Hollowood K, Birch J, Goodlad JR, Brenn T. Aberrant Melan‐A expression in atypical fibroxanthoma and undifferentiated pleomorphic sarcoma of the skin.