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Background Malignant tumor of the vulva is the fourth gynecological malignancy in frequency. Close to 70% of all vulvar malignancies are related to high-risk human papillomavirus (HPV) infection. Methods A search for non-HPV-related malignant tumors of the vulva was performed in the last 20 years (2000-2020) in the pathology database of a single tertiary institution. We aim to estimate the prevalence of non-HPV-related malignancies in our population, describe clinicopathological features of these tumors and investigate the expression of some potential therapeutic targets. Results A total of 71 patients were recovered; 26 patients (36%) had the diagnosis of extramammary Paget disease, 17 patients (24%) had basal cell carcinomas, 17 patients (24%) had primary melanomas, 10 patients (14%) had metastatic disease to the vulva and one patient (1%) had a primary dermatofibrosarcoma protuberans. Fifty-four percent of patients with extramammary Paget disease had a secondary malignancy and 12.5% had invasive disease. Programmed death-ligand 1 (PDL-1) was positive in seven out of nine primary melanomas and Her2/neu was overexpressed in six out of seven extramammary Paget disease. Conclusion Non-HPV-related malignancies are important differential diagnoses in patient with vulvar lesions. Additional research is necessary to further understand these complex malignancies and potential new therapeutic targets.

Dermatofibrosarcoma protuberans (DFSP) is a rare sarcoma of the skin arising from the dermis. Its location is most commonly presented on the trunk of middle-aged adults and rarely on the face. The characteristic genetic aberration in the form of a reciprocal translocation t(17;22)(q22;q13) or a ring fusing the COL1A1 and PDGFB genes is found in 90% of DFSP. We present a case of a 42-year-old man who presented with a DFSP on the left cheek with foci of myxoid- fibrosarcomatous transformation. A conventional chromosomal analysis revealed a complex karyotype without a supernumerary ring chromosome or a linear translocation t(17;22). Comparative genome hybridization (CGH) and fluorescence in-situ hybridization (FISH) revealed the fusion of COL1A1 and PDGFB probes inserted in chromosome 15. This is a unique case of DFSP characterized by a rare body location, unique histopathologic features and novel chromosome COL1A1-PDGFB insertion, and may help guide future diagnostic and patient care modalities. This article is protected by copyright. All rights reserved.

Medallion-like dermal dendrocyte hamartoma is a rare congenital lesion that is more commonly seen in females. It often presents at birth on the neck or upper trunk as a well-circumscribed, atrophic patch with wrinkling of the overlying skin. Clinically, the differential diagnosis includes atrophoderma, anetoderma, and congenital atrophic dermatofibrosarcoma protuberans. Histologic findings show epidermal atrophy and dermal spindle cell proliferation that is CD34 positive, along with Factor XIIIa in the original reports. Due to this CD34 positivity, another name for the lesion is plaque-like CD34+ dermal fibroma. We present a unique patient case as he is male and the lesion is located on his abdomen. Further reports and studies need to be done for thorough understanding of this neoplasm.

Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue tumor that arises primarily on the trunk and extremities but seldom on the scalp. Several variants of DFSP have been described, including myxoid DFSP. Although typical DFSP may have focally myxoid areas, myxoid DFSP, in which most of the stroma is myxoid, is rare and can pose diagnostic challenges. Here, we report a case of myxoid DFSP with an unusual clinical presentation that could have been mistaken for a lipoma. Additionally, the myxoid DFSP displayed prominent vasculature in a myxoid stroma, which could have been mistaken for a myxoid liposarcoma.

Dermatofibrosarcoma protuberans (DFSP) is a low-grade mesenchymal neoplasm with a tendency for local recurrence; it is rarely metastatic. Dermatofibrosarcoma protuberans typically arises in the trunk and proximal extremities. However, it can arise in unusual sites such as the hands and feet. Several variants have been described, including DFSP with myoid differentiation, which is very uncommon. This variant tends to be observed more with the fibrosarcomatous variant, and it can be either in the form of myoid bundles and nodules with no vascular relationship or represent hyperplastic blood vessels within the tumor. Here, we report 2 cases of DFSP with myoid differentiation (ordinary and fibrosarcomatous) on the foot. To the best of our knowledge, these cases represent the first 2 cases of acral DFSP with myoid differentiation.

Background Expression of p16 is frequently evaluated in melanocytic lesions. Expression of p16 in cutaneous histiocytic, fibrohistiocytic and undifferentiated lesions has not been well characterized. Methods We evaluated p16 expression in a cohort of histiocytic (reticulohistiocytoma, Langerhans cell histiocytosis, xanthogranuloma, Rosai Dorfman disease and xanthoma), fibrohistiocytic (dermatofibroma, epithelioid fibrous histiocytoma and dermatofibrosarcoma protuberans) and undifferentiated (atypical fibroxanthoma and pleomorphic undifferentiated sarcoma) lesions. A group of melanocytic lesions (Spitz nevus, ordinary nevus, spitzoid melanoma and non-spitzoid melanoma) were also evaluated as reference. Each case was scored by the proportion of p16-positive cells and by staining intensity. Results Immunoreactivity for p16 was found in almost all histiocytic (28/30, 93%) and fibrohistiocytic (22/24, 92%) lesions. About half of the undifferentiated lesions also exhibited p16 staining (9/17, 53%). Most of the melanocytic cases examined in this study expressed p16. A wide range of staining intensity and proportion of p16-positive cells was observed in most groups. Conclusion Expression of p16 is common, albeit variable in proportion and intensity, amongst a wide variety of cutaneous histiocytic, fibrohistiocytic and undifferentiated lesions. Further studies are required to determine if p16 expression is useful in distinguishing benign from malignant neoplasms of these types.

BACKGROUND Dermatofibrosarcoma protuberans (DFSP) is a tumor of intermediate malignancy, which in selected circumstances can pose difficulty in diagnosis. Clear cell sarcoma (CCS) is a very rare aggressive soft tissue sarcoma that can be difficult to distinguish histologically from melanoma. METHODS The current literature on t(17;22) COL1A1-PDGFB fluorescence in situ hybridization (FISH) assay in DFSP was reviewed. Also reviewed was the current literature on dual color break-apart EWSR1 FISH assay in CCS. Finally, the current utilization patterns of these tests was assessed in attendees of the American Society of Dermatopathology annual meeting (Chicago, 2016). RESULTS The literature indicates that (17;22) COL1A1-PDGFB FISH assay has limited value for classic DFSP, where the diagnosis can be established by routine morphology and immunohistochemistry. Given the high specificity of the EWSR1 FISH assay and significant complexity in the diagnosis of CCS, this ancillary study is helpful in distinguishing CCS from melanoma. CONCLUSIONS In attendees, t(17;22) COL1A1-PDGFB FISH testing for classic cases of DFSP is appropriately not being used by respondents. However, the literature sustains that it is useful in selected circumstances in which a definitive diagnosis is challenging. The majority of respondents are utilizing the EWSR1 FISH assay to distinguish CSS from melanoma as is supported by the literature.

Background: Cellular benign fibrous histiocytoma (CBFH) represents a morphologic variant of cutaneous fibrous histiocytoma (FH). Because of its relative monomorphism and frequent fascicularity, CBFH can easily be mistaken for a malignancy. In fact, CD34, often used to distinguish CBFH from dermatofibrosarcoma protuberans (DFSP), can also be positive. To add to the confusion, desmin positivity may also be observed in a subset of CBFH. Desmin and CD34 expression often cause interpretative difficulty which may lead to misdiagnosis. Our aim was to examine the incidence of desmin and CD34 expression in CBFH. Methods: One hundred consecutive cases of morphologically typical CBFH were retrieved from consultation files. Clinicopathologic and immunohistochemical features were evaluated. Results: SMA positivity was found in tumor cells in 93 of 100 cases (93%). Desmin positivity was found in 32 of 100 cases (32%). CD34 was positive in 6 of 100 cases (6%). There was no evident correlation between immunophenotype and anatomic site or other clinical variables. Conclusion: Frequent desmin (32%) and occasional CD34 (6%) expression are encountered in CBFH. Desmin positivity can be explained on the basis of myofibroblastic differentiation. The occasional CD34 positivity in a subset of CBFH should not be a deterrent from making the correct pathologic diagnosis, based on characteristic morphologic features.

We report two unique cases of dermatofibrosarcoma protuberans (DFSP) that included a pseudocystic component. Molecular analysis of one of the cases showed a characteristic COL1A1-PDGFB rearrangement in both the main tumor and also in the cells lining the pseudocystic portion of the tumor, confirming the diagnosis and indicating that the lining represented a component of the proliferation. It is important to raise awareness of this rare variant within the varied spectrum of DFSP. Shvartsbeyn M, Lazar AJF, Lopez-Terrada D, Meehan SA. Pseudocystic dermatofibrosarcoma protuberans: report of two cases and demonstration of COL1A1-PDGFB rearrangement.

CD10 is now commonly used to differentiate atypical fibroxanthoma (AFX) from melanoma, spindle cell and dedifferentiated variants of squamous cell carcinoma and leiomyosarcoma. However, we have encountered CD10-positive tumors that mimicked AFX but proved to be myxofibrosarcomas. The purpose of this study was to evaluate CD10 expression in a wide range of mesenchymal neoplasms that may involve the skin using tissue microarrays. Our results indicate that in addition to AFX, CD10 expression is common in myxofibrosarcomas, undifferentiated pleomorphic sarcomas, dermatofibromas and dermatofibrosarcoma protuberans. Myxofibrosarcomas commonly present in the skin and may be difficult to distinguish from AFX on small biopsies and CD10 positivity may confound the diagnostic difficulty.

The presence of multiple dermatofibromas is rare and is defined as more than 15 lesions. Multiple clustered dermatofibroma (MCDF) is a distinct entity with only 12 reported cases in the literature. MCDF occurs in healthy individuals of both sexes in the first to third decades on the lower half of the body and portends an excellent prognosis. On histology, MCDF is consistent with benign dermatofibromas. We report a 31-year-old healthy Hispanic woman with a 14-year history of slowly progressive MCDF located on her right hip initially misdiagnosed as dermatofibrosarcoma protuberans. We believe this case represents the 13th report of MCDF in the literature and the second from North America.

Over the past few years, a growing number of cutaneous tumors expressing CD34 is being reported. The list contains benign and malignant neoplasms as well as reactive and hamartomatous lesions of diverse lineages of differentiation, including fibroblastic, myofibroblastic, fibrohistiocytic, vascular, neural, adipocytic, smooth muscle, hematopoietic, melanocytic and epithelial. The more frequent diagnostic difficulties are found in spindle cell proliferations, mainly in those of the fibrocytic lineage. In part, this is because of the fact that in this area are, aside to well-defined entities, histologically and clinically diverse, recently reported cutaneous CD34-reactive lesions, whose definitions, limits and relationships are not completely established. The CD34 expression plays a key role in the differential diagnosis of some tumors, such as dermatofibrosarcoma protuberans, epithelioid sarcoma (ES) or pleomorphic hyalinizing angiectatic tumor of soft parts, with important therapeutic consequences. In others, as in desmoplastic trichilemmoma, it can help to resolve diagnostic problems in concrete cases. Finally, in many of the CD34-positive lesions, the diagnosis with the hematoxylin and eosin stain is straightforward. However, in all of them, the knowledge of the immunohistochemical profile contributes to our understanding of the cutaneous pathology.

We report a novel histological finding in a dermatofibrosarcoma protuberans (DFSP) after treatment with imatinib mesylate: copious amounts of hyalinized collagen. A 57-year-old female was referred for evaluation and treatment of a 7 x 8 x 10 cm tumor on the right anterior shoulder. Histological evaluation of the incisional biopsy showed a highly cellular dermal neoplasm composed of spindle cells arranged in a storiform pattern with minimal collagen. A CD34 immunohistochemical stain was strongly positive, highlighting atypical spindle cells in the dermis. A diagnosis of DFSP was made and the patient was enrolled in the Southwest Oncology Group trial. She received imatinib mesylate 400 mg per day for 1 year. At the end of therapy, the DFSP decreased in size to 5.5 x 4 x 4 cm. The tumor was excised. Histological evaluation showed a residual dermal neoplasm composed of atypical spindle cells and a copious amount of hyalinized collagen. Areas of necrosis were not seen. A CD34 stain confirmed the presence of residual DFSP, highlighting atypical spindle cells. A procollagen I stain was strongly positive, confirming the presence of abundant collagen in the dermis. A similar finding has been reported in gastrointestinal stromal tumor, which shows deposition of myxohyaline stroma after treatment with imatinib mesylate.

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive skin tumor. In addition to the conventional type, several morphologic variants have been described. Recognition of these uncommon variants will facilitate the diagnosis. We report herein a peculiar case of pigmented DFSP (Bednar tumor) with prominent meningothelial-like whorls, a distinctive pattern that has not been described previously in DFSP. The tumor occurred in a 40-year-old man who presented with a slowly growing mass on his left shoulder. The overall histological features were consistent with Bednar tumor. However, unexpected numerous meningothelial-like whorls were found in some areas of the tumor. Like the tumor cells in typical areas of Bednar tumor these meningothelial-like whorls were also positive for CD34 but negative for epithelial membrane antigen and S100 protein. The meningothelial-like whorls in Bednar tumor represent an eccentric arrangement of the tumor cells. We propose the term 'pigmented DFSP with prominent meningothelial-like whorls' to highlight the distinctive pattern of this novel DFSP variant.

According to most authors, dermatofibrosarcoma protuberans (DFSP) and giant cell fibroblastoma (GCF) represent the adult and juvenile forms, respectively, of the same disease entity, as evidenced by similar morphology, an identical chromosomal translocation, and CD34 positivity. It has been shown that DFSP and nuchal-type fibroma (NTF) (which is also CD34-positive) are related lesions, and that there might possibly be a continuum between the two. In addition, NTF exhibits CD99 positivity. It was therefore, hypothesized that both DFSP and GCF would show similar immunopositivity for CD99. Archives of pathology at several institutions were searched for DFSP and GCF tissue blocks. A total of 29 DFSP and 5 GCF were analyzed by immunohistochemistry for expression of CD99. Twenty-three of 29 DFSP (79%) and 2 of 5 GCP (40%) expressed CD99. Comparison of CD99 and CD34 showed that the non-tumoral periphery of DFSP was less probable to be CD99 positive, but this finding was not statistically significant.

Background: Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) occasionally resemble each other histologically but differ in histogenesis and biological behavior. This study sought to determine if these lesions can be differentiated by the quantity or quality of expression of cyclooxygenase-2 (COX-2), an enzyme associated with both reactive and neoplastic processes. Patients and methods: Formalin-fixed and paraffin-embedded samples from 20 DFs and 20 DFSPs were stained immunohistochemically with antibodies directed against COX-2. Staining was evaluated semiquantitatively for percentage and intensity using a three-tiered system. DFs were graded and analyzed by cellularity. Findings within the tumors were compared with fibrocyte staining in adjacent tissue. The results were analyzed. Results: Nineteen DFs (95%) and 15 DFSPs (75%) were immunopositive for COX-2; this difference was not statistically significant. Highly cellular DFs showed more widespread (p = 0.0039; r = 0.614) and more intense (p = 0.0586; r = 0.429) staining than less cellular DFs and more prominent staining in adjacent fibroblasts (p = 0.044; r = 0.608). Conclusions: COX-2 immunostaining does not distinguish DFs from DFSPs. However, the enzyme is expressed more widely and more intensely in more cellular, possibly younger, DFs. The prominent expression of COX-2 in DFSP may have clinical implications for treatment with COX-2 inhibitors in tumors that are not amenable to surgery.

Background: Dermatofibrosarcoma protuberans (DFSP) is a relatively uncommon spindle cell tumor of the skin. It is locally aggressive and can be a therapeutic challenge. There are case reports of partial response of DFSP to the tyrosine kinase inhibitor STI571 (Imatinib), despite the reported negativity of the tumor cells for CD117. At least one publication reported focal CD117 positivity of DFSP cells, and we would like to clarify the issue. Cellular dermatofibroma (CDF) can mimic DFSP, but typical cases are easily differentiated from DFSP by their staining pattern for CD34 and factor 13a. We also report our experience with CD117 staining of typical CDFs. Methods: Thirty-seven cases of clear-cut DFSP and 13 cases of clear-cut CDF were retrieved from the archives of Sunnybrook Health Sciences Center between 2000 and 2005. Results: All DFSPs were CD34 (+), factor 13a (−) and CD117 (−). All CDFs were factor 13a (+), CD34 (−) and CD117 (−). Conclusions: Our study on a relatively large number of cases confirms the negativity of DFSP and CDF for CD117. Therefore, if adjuvant therapy is attempted with drugs such as STI571 (Imatinib), the eligibility of patients should not be based on immunohistochemical assessment of CD117 expression.

Background Distinction between cellular fibrous histiocytomas (FHs) with a deep component and dermatofibrosarcoma protuberans (DFSPs) can pose diagnostic problems. While CD68, CD34, and Factor XIIIa are helpful in distinguishing between these entities, none are diagnostically absolute. Recent work with CD163, a hemoglobin scavenger receptor, has demonstrated that this marker has high specificity for monocytes, macrophages, and histiocytes. Our goal is to evaluate the utility of CD163 in the diagnosis of dermatofibromas (DFs), cellular FHs, and DFSPs. Methods Sixty cases including 19 DFs, 23 cellular FHs with a deep component, and 18 DFSPs were tested with antibodies against CD163, CD68, CD34, and Factor XIIIa. Results CD163 was expressed in 17/19 (89%) DFs, 23/23 (100%) cellular FHs, and 3/18 (17%) DFSPs. CD68 was positive in 8/19 (42%) DFs, 19/23 (83%) cellular FHs, and 1/16 (6%) DFSPs. CD34 was expressed in 1/19 (5%) DFs, 5/23 (22%) cellular FHs, and 100% of DFSPs. Factor XIIIa labeled 4/19 (21%) DFs, 11/23 (48%) cellular FHs, and 0/17 cases of DFSPs. Conclusions CD163 expression is helpful in distinguishing between cellular FHs and DFSPs and will be useful in a panel of antibodies when these entities are in the differential diagnosis. Sachdev R, Sundram U. Expression of CD163 in dermatofibroma, cellular fibrous histiocytoma, and dermatofibrosarcoma protuberans: comparison with CD68, CD34, and Factor XIIIa.

Background: CD44 is a membrane glycoprotein and the major cell-surface receptor of hyaluronate (HA). Lack of CD44 expression in mouse epidermis leads to an abnormal HA accumulation in the dermis, indicating an important role of CD44 in local HA metabolism. Decrease of epidermal CD44 expression in patients of lichen sclerosus et atrophicus is potentially responsible for dermal deposition of HA in this disease. Stromal HA accumulation is associated with decreased or lost expression of CD44 in perifollicular solitary cutaneous myxoma, myxoid dermatofibroma, and dermatofibrosarcoma protuberans. Methods: We examined the expression of CD44 and HA in the skin biopsy specimens of 10 patients with follicular mucinosis by using CD44-specific antibodies and biotinylated HA-binding protein (HABP), respectively. Results: No difference of CD44 expression was observed in the follicular keratinocytes when compared with those of unaffected interfollicular epidermis. The follicular zones of mucin deposition were strongly positive for HA. A weak interkeratinocyte staining for HA was also observed in the interfollicular epidermis. However, HABP staining revealed a stronger reactivity in the follicular keratinocytes surrounding the mucin-accumulated areas compared to the interfollicular keratinocytes. Conclusion: Our results suggest an active secretion of HA by follicular cells in follicular mucinosis.

Background: Digital fibromas are common benign acral tumors typically reported as angiofibromas (AFs) or acquired digital fibrokeratomas (ADFs). Cellular variants are not well recognized. Methods: We collected 14 acral fibrocytic lesions showing a spindle cell morphology from our files, and evaluated CD34, Factor XIIIa, epithelial membrane antigen (EMA), and S100 protein staining of these lesions. We compared the histologic and immunohistochemical features of these cellular fibromas with five digital AFs, five ADFs, and five digital dermatofibromas. Results: The 14 cellular digital fibromas showed intersecting fascicles of thin delicate bland spindle cells in the superficial reticular dermis with a fibrotic-to-slight myxoid stroma. The spindle cells in all cases stained strongly for CD34, and only scattered stromal cells stained for Factor XIIIa. Five tested cases were negative for EMA and S100 protein. The digital AFs, fibrokeratomas, and dermatofibromas stained predominately for Factor XIIIa, with no or minimal staining for CD34. Conclusions: These findings suggest that a subset of digital fibromas is characterized by a dense cellular proliferation of CD34-positive spindle cells. Awareness of this variant of digital fibroma and its staining pattern is critical in preventing misdiagnosis as dermatofibrosarcoma protuberans, particularly in superficial biopsies.

Background: Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignant neoplasm that has the potential for aggressive local growth and destruction if not treated appropriately. Although the storiform arrangement of spindle cells in DFSP is relatively characteristic, histologic patterns simulating other benign as well as malignant neoplasms such as dermatofibroma, neurofibroma, malignant fibrous histiocytoma, and atypical fibroxanthoma have been described. Methods: We collected and analyzed six cases of probable DFSP in which a specific diagnosis could not be rendered due to the predominant neurofibromatous changes in the histologic sections. In an attempt to reach a definitive diagnosis, the clinical history and physical characteristics of the lesions were taken into account, and all cases were further evaluated using immunostaining for CD34 and S-100 protein. Results: The average age of the patient was 56 years (range 21–80), and the male to female ratio was 1 : 1. The location of lesions included the scalp, neck, back, and abdomen. All cases displayed two distinct histological patterns: (i) a proliferation of spindle cells with wavy nuclei in a loose mucinous stroma suggesting neural differentiation and (ii) a proliferation of spindle cells which interweaved and filled the reticular dermis extending into the subcutis. The wide variety of clinical impressions and descriptions indicated that the diagnoses were not always straightforward, and clinical information did not always assist in the clinicopathologic correlation. All lesions stained positively for CD34; however, three of six cases also stained positively for S-100. The three cases which were CD34 positive and S-100 negative were likely DFSP, and this was the final diagnosis given. The three cases that were CD34 and S-100 positive did not allow for a straightforward diagnosis. Conclusions: DFSP may demonstrate areas with features more characteristic of a benign neural lesion, such as a neurofibroma, which can lead to underdiagnosis and subsequent failure to treat. Clinicians and pathologists should recognize this potential diagnostic pitfall and understand that equivocal clinical information, combined with non-specific immunohistochemical staining patterns, can further complicate the dilemma. In these situations, where DFSP is the likely diagnosis but definitive evidence cannot be obtained, full excision of the lesion should be recommended to avoid mistreatment of a potentially malignant lesion.

Aim: This study was undertaken to assess whether heat-shock protein (HSP)47 is a useful cell marker for skin fibroblasts in formalin-fixed, paraffin-embedded skin specimens. Background: HSP47, a 47-kDa HSP, is a collagen-specific molecular chaperone localized in the endoplasmic reticulum. HSP47 plays an essential role in collagen biosynthesis in skin fibroblasts. Methods: Immunohistochemistry was performed to detect HSP47 in skin fibroblast cultures and skin tissue sections. Results: Immunostaining for HSP47 clearly detected skin fibroblasts in paraffin tissue sections as well as in fibroblast cultures and frozen tissue sections. HSP47 staining on paraffin sections from diseased skin specimens revealed that skin ulcer, keloid, nodular fascitis, spindle cell lipoma, and dermatofibroma had strong signals for HSP47 compared with the signals obtained from normal skin. Dermatofibrosarcoma protuberans had many HSP47 positive cells, but signals on individual cells were not as strong as those seen from the above benign proliferative disease samples. In neurofibroma, a small number of faintly positive cells were detected. Our double-immunostaining studies also demonstrated that HSP47 staining distinguished skin fibroblasts from CD68-positive histiocytes/macrophages, factor VIII-related antigen-positive endothelial cells, or factor XIIIa-positive dermal dendritic cells. CD34-positive interstitial cells coexpressed HSP47 in spindle cell lipoma. Conclusions: These findings indicate that HSP47 staining can detect skin fibroblasts in routine, paraffin-embedded specimens. A panel approach using HSP47 and other cell markers on paraffin sections may help the identification of the cell type involved with mesenchymal proliferative disorders.

Background: Dermatofibrosarcoma protuberans (DFSP) is a hypercellular, storiform, CD34-positive low-grade sarcoma with honeycomb entrapment of fat, which typically involves the trunk and extremities. Nuchal-type fibroma (NTF ) is a paucicellular, CD34-positive fibrous tumor with fat entrapment, which may occur in both nuchal and extranuchal locations and in association with Gardner syndrome. Methods: We report the association of DFSP with NTF in a 43-year-old male with no personal or family history of Gardner syndrome. Results: The patient had a past history of a DFSP removed from his back, which recurred 2 years later and was re-excised. Additionally, the patient had a typical NTF, in the posterior neck, removed at the same time. Histopathologic examination of the recurrent back lesion demonstrated a composite lesion with typical appearances of DFSP, centrally, blending into an NTF-like appearance, peripherally. Both components expressed CD34 and CD99, and lacked elastin. A review of the microscopic slides of the patient's previously excised DFSP revealed an identical lesion with surrounding NTF-like areas. Conclusion: While an association between NTF and fibromatosis has recently been reported, this is to our knowledge the first report of an association between NTF and DFSP. The morphologic findings suggest that there may be a continuum between these two CD34-positive lesions that have a tendency to infiltrate adipose tissue and recur.

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.

Background: Dermatofibrosarcoma protuberans (DFSP) is an uncommon infiltrative tumor of the dermis with characteristic cytogenetic features, specifically the translocation t(17;22)(q22;q13) which often manifests as a supernumerary ring chromosome r(17;22). The translocation results in the fusion of two genes, collagen type I alpha 1(COL1A1) and platelet-derived growth factor B-chain (PDGFB). The trunk and extremities are the anatomic sites of predilection for DFSP, whereas the vulva and groin are quite uncommon sites of involvement. Methods: This investigation evaluated seven DFSPs (four vulvar and three groin) for the presence of COL1A1-PDGFB fusion transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR), using archival formalin-fixed, paraffin-embedded tissue. Results: Six of seven cases (three vulvar, three groin) contained a COL1A1-PDGFB fusion transcript. Sequence analysis of the PCR products revealed that the break-point of the COL1A1 gene was located after exon 40 in two patients, after exon 42 in one patient, after exon 44 in one patient, and after exon 47 in two patients; the break-point in the PDGFB gene was before exon 2 in all cases. No fusion transcript could be amplified in one case. Conclusions: As in DFSP at other sites, COL1A1- PDGFB chimeric fusion transcripts are present in vulvar and groin DFSP. The transcripts can be detected in formalin-fixed, paraffin-embedded tumor tissues, and have the same general pattern of exon boundaries as in DFSP at other sites.

Background: Neuroectodermal differentiation or melanocytic colonization are the opposing theories of histogenesis for the Bednar tumor or pigmented dermatofibrosarcoma protuberans (DFSP). Observation: A 31-year-old African-American woman presented with a 2-cm blue-black shoulder nodule of 1-year duration. Punch biopsy revealed a CD34+, Factor XIIIa-DFSP, harboring numerous, pigmented spindle S100+, Mart-1+ and HMB-45+ cells. Subsequent wide excision demonstrated pigmented dendritic and spindled cells widely scattered throughout the dermis of the 3-cm excisional margins and punch biopsy specimens of normal skin from both shoulders. This latter process was interpreted as dermal melanocytosis (nevus of Ito). The dermal pigmented spindle cells were Mart-1+ and CD34−, and were associated with non-pigmented CD34+, cytologically banal spindle cells, which were more numerous in the excisional margins than the contralateral shoulder. Conclusion: Reported herein is a singular case of Bednar tumor associated with dermal melanocytosis. Although the coexistence of these processes implicates colonization of the DFSP by constituent dermal melanocytes, the mixed immunophenotype (CD34+ or Mart-1+ cells) of dispersed dermal spindle cells hints at the possibility of a common cell of origin: the putative neuromesenchymal cell. In effect, the Bednar tumor could represent one part of a spectrum of neural crest-derived dermal tumors that includes dermal melanocytosis, cellular blue nevus and conventional DFSP.

Background: Dermatofibroma (DF) or cutaneous fibrous histiocytoma is a common benign fibrohistiocytic lesion involving the dermis and subcutis. Histologically, it is subclassified into fibroblastic and histiocytoid forms. Its histogenesis is controversial. While often referred to as a neoplastic process, definite evidence of neoplasia in DF has been lacking. Alternatively, some authorities have suggested that DF is a fibrosing inflammatory process. Diagnostically, the most important question faced is the distinction from dermatofibrosarcoma protuberans (DFSP). Misdiagnosis can occur, as the early phase of DFSP can simulate DF, particularly the deep and cellular forms of DF. Methods: To address this issue, and to investigate whether DF is in fact a neoplasm, we evaluated 31 examples of DF of various histological types in female patients and assessed clonality by analyzing X-chromosome inactivation as indicated by the methylation status of the androgen receptor gene (HUMARA). Representative cases of DFSP were analyzed for comparison. Results: Among the selected 31 cases of DF, 24 cases provided intact DNA and informative polymorphism at the AR alleles, including one case of recurrent deep fibrous histiocytoma. Among these 24 cases, randomly inactivated AR alleles were observed in 17 cases including a deep, recurrent fibroblastic DF. A non-random inactivation at AR alleles was observed in seven cases, of which six cases showed either typical histiocytoid form of DF (four cases) or mixed cell types with predominant histiocytoid cell type (two cases). One fibroblastic DF also showed a monoclonal pattern. HUMARA analysis of DFSP revealed non-random inactivation of polymorphic AR alleles. Conclusions: These findings suggest that DF is a heterogeneous process. Monoclonal genotype was found in DFs with histiocytoid or mixed type with predominant histiocytoid features, suggesting that histiocytoid cells probably represent the neoplastic component. The fibroblastic form of DF may represent a reactive fibroblastic proliferation. Alternatively, it may represent a true neoplasm whose neoplastic cell type has been obscured by prominent reactive fibroblastic component.

Background: Scars are commonly encountered by dermatopathologists and usually do not present a diagnostic challenge. However, in some cases, the pathologist may need to consider a broad differential diagnosis including fibrohistiocytic tumors, smooth muscle tumors, myofibroblastic proliferations and desmoplastic malignant melanoma. Although specific histologic aspects of scars have been well studied, a complete histochemical profile of scars, especially at various stages of evolution, has not been described. Methods: Twenty-five cases of scars including 8 normal scars, 5 hypertrophic scars and 12 keloids were studied. Sections were examined with Verhoeff van Giesson, colloidal iron, Giemsa, smooth muscle actin (SMA), CD34, Factor XIIIa and S-100. Results: All scars were negative for CD34 expression. Factor XIIIa immunostaining identified only rare dermal dendrocytes. S-100 was absent in 23 of 25 cases and stained scattered cells (less than 10%) in the other 2 cases. SMA was positive in 14 of 25 cases with 6 of these showing staining of up to 50% of spindled cells. Elastic fibers were markedly reduced or absent in all cases, mucin showed moderate or marked staining in three-fourths of the cases and dermal mast cells showed a moderate increase in 5 cases. Conclusions: These findings confirm prior reports that negative staining with CD34, Factor XIIIa and S-100 can help differentiate scars from dermatofibrosarcoma protuberans, dermatofibroma and desmoplastic malignant melanoma, respectively. SMA staining is much more variable and requires careful interpretation.

Background: Primary and metastatic malignant melanoma can simulate various soft tissue tumors, including dermatofibrosarcoma protuberans (DFSP). Expression of CD34, a marker characteristic of DFSP, as well as other spindle cell tumors, has not been previously documented in malignant melanoma. Methods: We present here an unusual case of metastatic malignant melanoma with a strong histologic resemblance to DFSP and also CD34 expression. Results: The patient, a 72-year-old man with a history of an invasive malignant melanoma of the skin of the right lower abdomen, presented with a right axillary mass. Histologic sections revealed intersecting fascicles of spindle cells with nuclear pleomorphism and numerous mitotic figures, diffusely infiltrating the adipose tissue in a pattern closely simulating that seen in DFSP. In other foci, epithelioid neoplastic cells with abundant cytoplasm, prominent nucleoli, nuclear pseudoinclusions, and focal cytoplasmic melanin pigment were seen. The neoplastic spindle cells were strongly labeled by two anti-CD34 monoclonal antibodies. Some of the spindle cells and the majority of the epithelioid neoplastic cells expressed S-100 protein and focally tyrosinase. The tumor cells were negative for HMB-45 and MART-1. Melanosomes were not identified by electron microscopy. Conclusion: This case demonstrates the potential of melanoma to simulate DFSP closely, on both morphologic and immunohistochemical grounds, and confirms the utility of employing a broad panel of immunohistochemical reagents in problematic cases.

Background: S100A6, an S100 calcium-binding protein, has been found in a variety of cutaneous and extracutaneous lesions including: melanocytic nevi, melanoma, some salivary gland and epithelial tumors, and malignant fibrous histiocytoma (MFH). Dermal dendrocytes (DD) in the papillary dermis of skin also express S100A6 protein. We evaluated a variety of cutaneous fibrohistiocytic lesions to determine if the immunophenotype of S100A6 positivity can be expanded to include some or all of these lesions. Methods: Formalin-fixed, paraffin-embedded tissues from fibrous papules (FP, 20), dermatofibromas (DF, 20), dermatofibrosarcoma protuberans (DFSP, 5), atypical fibroxanthomas (AFX, 5), oral fibromas (3), digital fibroma (1), and dermatomyofibroma (1) were evaluated with antibodies to S100A6, S100B, factor XIIIa, and MAC387 using a one-hour capillary action-based immunohistochemical procedure. Results: DD in 20/20 FP, 19/20 DF, and 4/4 fibromas stained positively with anti-S100A6 in a pattern similar to anti-factor XIIIa. No DFSP cases stained with anti-S100A6. Anti-S100A6 showed superior staining to anti-factor XIIIa in 4/5 AFX cases. Conclusions: The immunophenotypes of some fibrohistiocytic lesions can be expanded to include S100A6 protein. With the exception of AFX, the use of anti-S100A6 does not appear to offer added benefit over anti-factor XIIIa in the differential diagnosis of fibrohistiocytic lesions.

Dermatofibrosarcoma protuberans (DFSP) is a fibrohistiocytic tumor of intermediate malignancy characterized by a distinctive storiform growth pattern and frequent local recurrences. In this study, we retrospectively reviewed 48 cases of DFSP diagnosed at the Cleveland Clinic Foundation between 1970 and 1999 to determine the prevalence of morphologic variations including the presence of giant cell fibroblastoma (GCF)-like areas, multinucleated giant cells, hypercellular zones and fibrosarcomatous change. Results: The cohort consisted of 42 patients (20 males, 22 females) with a median age at diagnosis of 40 years (range: 10-73 years). Forty-one primary tumors and seven recurrences were evaluated from these 42 patients. Tumor sites included the trunk (22 cases), head and neck (8 cases), upper extremities (7 cases) and lower extremities (6 cases). GCF-like areas were identified in seven (14.6%), multinucleated giant cells in ten (20.8%), hypercellular zones in 12 (25%) and fibrosarcomatous change in six (12.5%) cases, respectively. Combinations included giant cells and GCF-like areas (two cases), giant cells and hypercellular zone (two cases), and GCF-like areas and hypercellular zones (one case). Our findings suggest that DFSP has a wider range of morphologic features, including GCF-like areas, multinucleated giant cells, hypercellular zones and fibrosarcomatous change, than has been previously recognized in the literature.

Two uncommon cases of dermatofibrosarcoma protuberans with prominent myxoid changes are presented. The tumors appeared as large multinodular cutaneous plaques that arose at the sites of excision of previous tumors some years earlier. In addition to limited fibrous storiform features, focally observed in deep and peripheral portions of the tumors, a diffuse myxoid pattern could be observed. The latter consisted of homogeneous areas of rare, stellate or spindle-shaped cells, haphazardly scattered in abundant myxoid matrix. Cells of myxoid neoplastic tissue showed mainly a positive immunoreaction for fibrohistocytic markers and the absence either of muscular, neural or human progenitor cell antigens. Mitotic figures were fewer and cell proliferation rates were lower in myxoid as compared to those of typical dermatofibrosarcoma protuberans used as a control. The ultrastructural examination of myxoid areas revealed a prevalent fibroblast-like cell population showing dilated cytoplasmic vesicles, sometimes containing glycosaminoglycans-like substances. The extent of myxoid changes together with the characteristic morphological, ultrastructural and immunohistochemical features confirm that myxoid dermatofibrosarcoma protuberans is a distinct variant of this fibrohistiocytic tumor to be considered in the differential diagnosis among myxoid tumors of the skin.

This unusual case is that of a middle-aged man exhibiting a tumor diathesis including a basal cell adenocarcinoma with features of adenoid cystic carcinoma arising in minor salivary gland of lip in association with multiple primary malignant cylindromas of skin. The labial lesion showed invasive tubules, solid epithelial sheets and cribriform structures. It did not exhibit PAS positive juxta-tubular basement membrane material. The skin lesions all showed features of a highly infiltrative cylindromatous carcinoma with two cell types, peripheral palisading and prominent PAS positive juxta-tubular basement membrane material. Immunocytochemical studies of the lip lesion and one of the skin lesions showed similarities, including positive staining for high and low molecular weight keratins and S-100 with negative staining for CEA. The precious descriptions of tumor diatheses involving dermal cylindromas and dermal analogue tumors of salivary glands and the distinctions with the present study are noted. If benign and even malignant cylindromas were described in the literature to be associated with basal cell adenocarcinoma of the major salivary glands, our case is unique by its association with this rare malignant tumor in a minor salivary gland.