Cutaneous soft tissue tumors: how do we make sense of fibrous and "fibrohistiocytic" tumors with confusing names and similar appearances?

In the 2018 World Health Organization Classification of Skin Tumors, a wide range of predominantly benign mesenchymal neoplasms are included in the fibroblastic, myofibroblastic, and "fibrohistiocytic" categories. By far the most common of these tumors is dermatofibroma (fibrous histiocytoma). There are many histologic variants of dermatofibroma, some of which (cellular, aneurysmal, and atypical) are associated with a higher risk of local recurrence; these variants may be mistaken for more aggressive tumor types, including sarcomas. Furthermore, distinguishing among the fibrous and "fibrohistiocytic" tumors can be a diagnostic challenge, given their sometimes-similar histologic appearances and confusing nomenclature. Immunohistochemistry and molecular genetic assays play a relatively limited role in the diagnosis of these tumor types, with notable exceptions (i.e., epithelioid fibrous histiocytoma and dermatofibrosarcoma protuberans). Proper recognition of dermatofibrosarcoma protuberans is critical, since this tumor type is associated with locally aggressive behavior; transformation to the fibrosarcomatous variant brings metastatic potential. In recent years, understanding of the molecular pathogenetic basis for cutaneous mesenchymal neoplasms has increased dramatically, with the discovery of gene rearrangements in some of these tumor types. In this review, the histologic features of the most common fibrous and "fibrohistiocytic" cutaneous mesenchymal neoplasms will be discussed, as well as recently identified molecular genetic alterations.

Collagen Features of Dermatofibrosarcoma Protuberans Skin Base on Multiphoton Microscopy.

Dermatofibrosarcoma protuberans is a rare, low-grade skin fibroblastic tumor which tends to recur locally due to its high misdiagnosis. Dermatofibrosarcoma protuberans usually spreads through the intracutaneous and subcutaneous layers into the deep dermis layer in which the main component is collagen. Therefore, alterations in collagen shape and content are important for accurate diagnosis of dermatofibrosarcoma protuberans. In this study, multiphoton microscopy was employed to observe normal human skin and dermatofibrosarcoma protuberans skin. Then, a centerline based on an algorithm that skeletonizes a binary image of fibers was applied to analyze collagen shapes in 2 types of skin. Then, collagen content, including intensity and density, was quantitatively obtained to demonstrate differences between the 2 skin types. Results indicate that collagen shape and density can be considered as auxiliary diagnostic parameters to improve the accuracy of dermatofibrosarcoma protuberans diagnosis.

Dermatofibrosarcoma Protuberans of Distal Extremities and Acral Sites: A Clinicopathologic Analysis of 27 Cases.

Dermatofibrosarcoma protuberans (DFSP) of the distal extremities and acral sites are extremely rare and incompletely characterized. Twenty-seven DFSP occurring in these sites were retrieved from our collective archives and reevaluated. Tumors occurred in 16 males and 11 females. Median age at presentation was 42.5 years (range, 7 to 78 y). Lesions involved the foot (18 with 6 in the toes and 2 on the plantar foot), distal ankle (4), hand (4 with 2 in the thumbs), and wrist (1). All cases showed predominantly classic DFSP morphology and were diffusely CD34 positive. Myxoid change, melanin pigmented, and giant cell fibroblastoma foci were each present in 1 case, respectively. Fibrosarcomatous change was present in 3 cases. Fluorescent in situ hybridization demonstrated PDGFB gene rearrangement in 9 of 10 tested cases. Clinical follow-up was available in 21 cases (median, 36.1 mo; range, 1 to 152 mo) and revealed 4 local recurrences. Four patients underwent digital amputation for unresectable recurrent disease. An additional patient underwent multiple resections with positive margins and elected to receive imatinib mesylate therapy. After a 2-year course, the patient has no evidence of residual disease (40 mo). No metastases were documented in any of the cases studied. The natural history of DFSP of distal extremities and acral sites is similar to that of its counterparts elsewhere. A high index of suspicion, careful morphologic examination for key histologic features of DFSP, and in selected cases, molecular studies to identify the pathognomonic COL1A1-PDGFB gene fusion should facilitate the distinction of these rare, locally aggressive neoplasms from morphologic mimics that may arise in distal extremities and acral sites.

Hormone receptor expression in patients with dermatofibrosarcoma protuberans.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma for which the exact etiology is unknown. Case reports exist of DFSP appearing and growing rapidly during pregnancy, suggesting a hormonal role. OBJECTIVE: Our goal was to determine the expression of estrogen receptors (ERs) and progesterone receptors (PRs) in patients with DFSP. METHODS: Archived formalin-fixed, paraffin-embedded tissue from patients with DFSP in the past 20 years at a single institution were analyzed for ER and PR using immunohistochemistry. A semiquantitative scoring method was used to evaluate the expression as positive or negative. Analysis was used to determine whether there was an association between receptor positivity and tumor site, age at diagnosis, sex, race, or disease recurrence. RESULTS: Forty-four patients with DFSP were included in the study. Tumors were 22.7% ER+/PR+, 34.1% ER+/PR-, 9.1% ER-/PR+, and 34.1% ER-/PR-. There was no significant association between expression of ER and PR and sex, age at diagnosis, race, or tumor location. Loss of receptor expression was observed in all recurrent tumors. LIMITATIONS: This study is limited by a lack of follow-up and a new scoring system. CONCLUSIONS: The data presented warrant additional study to determine hormone receptor function and the potential efficacy of antihormone therapies for the treatment of patients with DFSP.

Polarized Microscopy in Lesions With Altered Dermal Collagen.

Alterations in dermal collagen are noted in dermatofibroma, dermatofibrosarcoma protuberans, morphea, lichen sclerosus et atrophicus, hypertrophic scars, and keloids. The authors sought to determine whether variations in birefringence of collagen by polarized microscopy could be of help in diagnosing such conditions. Representative hematoxylin and eosin sections of 400 cases, including dermatofibroma, dermatofibrosarcoma protuberans, hypertrophic scars, keloid, morphea, and lichen sclerosus, were examined under polarized microscopy. Distinct patterns of birefringence of collagen for each disease were noted under polarized microscopy. This study highlights the use of polarized microscopy as adjunctive tool in differentiating different diseases with collagen alteration.

Congenital atrophic dermatofibrosarcoma protuberans detected by COL1A1-PDGFB rearrangement.

BACKGROUND: Atrophic variant of dermatofibrosarcoma protuberans (DFSP) is a distinct form of DFSP. CASE PRESENTATION: Here, we report the case of a 19-year-old woman with a small congenital atrophic plaque on the right precordium. The lesion remained atrophic for more than 10 years. Several years earlier, a portion of the plaque became tuberous and enlarged. Physical examination revealed a 25 × 30 mm erythematous atrophic plaque surrounded by three hard, smooth, and orange-colored nodules of varying sizes on the right precordium, along with visible subcutaneous adipose tissue and cutaneous veins. Biopsy of the nodule and atrophic plaque revealed dense proliferation of spindle-shaped tumor cells from the dermis to the subcutaneous adipose tissue, and positive immunostaining for CD34 and vimentin in addition to negative staining for factor XIIIa and α-smooth muscle actin. Reverse transcription polymerase chain reaction (RT-PCR) of the tumor tissue revealed the presence of a COL1A1-PDGFB fusion gene. Thus, congenital atrophic dermatofibrosarcoma protuberans was diagnosed. No metastasis to the lungs or regional lymph nodes was found on magnetic resonance imaging. Wide local excision and split-thickness skin grafting was performed and neither recurrence nor metastasis has been observed for 5 years and 8 months since the surgery. CONCLUSION: This case indicates that a congenital atrophic lesion could represent a quiescent phase of DFSP. Awareness of this rare condition can aid with early diagnosis and thereby improve the prognosis of DFSP.

Palisading and Verocay body-prominent dermatofibrosarcoma protuberans: A case report.

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma with a tendency for local recurrence, which commonly presents as a slowly growing flesh-colored skin lesion without epidermal invasion but with intracutaneous and subcutaneous spread. Pathologically, the tumor generally presents with an infiltrating dermal mass containing closely packed fibroblasts arranged in a storiform pattern. Several uncommon growth patterns have been described, including sclerosing, atrophic, myxoid, pigmented, giant cell-rich, granular cell, herringbone pattern and palisading/Verocay body-prominent forms. To our knowledge, only five cases of DFSP with nuclear palisading/Verocay body formation have been reported in the literature, and no t(17:22) translocation study has been done on these cases. In this report we describe such a case with negative t(17:22) translocation.

Giant Hemosiderotic Dermatofibroma: The Largest Giant Dermatofibroma Reported to Date.

Dermatofibroma (DF) is a relatively common benign fibrohistiocytic soft tissue tumor. It has a slightly greater incidence amongst females and typically presents itself during the midadult life as a slowly growing, firm dermal nodule, usually smaller than 2 cm in diameter, on the lower extremities. Giant DF is a rare clinical variant of DF characterized by unusually large size (>5 cm), which mimics malignant soft tissue tumor clinically. Twenty-six cases of giant DF have been reported so far. One of these giant DFs was a giant hemosiderotic DF. We report herein a case of a 47-year-old woman who presented with the largest DF reported in the literature to date. It was hemosiderotic.

Deep dermatofibrosarcoma protuberans in a ninety-year old-woman.

A 92-year-old woman was referred for the assesment of an asymptomatic subcutaneous tumor that developed after an accidental fall. The mass clinically and radiologically simulated a subcutaneous hematoma. Finally, the histological study was consistent with subcutaneous dermatofibrosarcoma protuberans.

Braided pattern in a dermatofibrosarcoma protuberans: a potential mimicker of neural neoplasms.

Dermatofibrosarcoma protuberans (DFSP) is a dermal and subcutaneous slow-growing tumor of intermediate malignancy. Different histological variants of DFSP have been described, depending on cellular and stromal peculiarities. Here, we report the histological features of a DFSP in which cells were frequently arrayed in cords and fascicles that were interweaved, conforming a peculiar braided pattern. This finding might pose difficulties in the differential diagnosis with neural neoplasms and expands the morphological spectrum of DFSP.

Primary dermatofibrosarcoma protuberans of orbit--a rare entity.

Primary Dermatofibrosarcoma Protuberance (DFSP) is a rare neoplasm of dermal origin. Though it is a locally aggressive tumor with high recurrence rate, however distant metastasis can also occur. Orbital DFSP is an uncommon phenomenon. It has been reported due to distant metastasis or invasion from adjacent structures but Primary Orbital DFSP is a unique entity in itself. Herein we report a rare case of primary DFSP of the orbit in a 70-year- old lady who underwent orbital exenteration. Histopathology examination (HPE) revealed spindle cells arranged in storiform pattern and immunohistochemistry (IHC) revealed CD34 positive and S100 negative.

Dermatofibrosarcoma protuberans with primary orbital manifestation.

A 45-year-old, otherwise healthy woman presented with mild epiphora and a palpable mass in the lacrimal sac area. After transcutaneus orbitotomy and complete excision histopathology revealed a primary Dermatofibrosarcoma protuberans invading the orbit. During the 24-months follow-up, no recurrence occurred. To the best of our knowledge this is the first report of a primary DFSP with the orbit involved.

Atrophic dermatofibrosarcoma protuberans: report of a case demonstrated by detecting COL1A1-PDGFB rearrangement.

Dermatofibrosarcoma protuberans is a locally aggressive mesenchymal neoplasm. It usually presents as an indurated plaque that protrudes above the surface of the skin. Some patients have clinically persistent plaques that might be atrophic. The atrophic variant of dermatofibrosarcoma protuberans may be confused with some common skin diseases with atrophic appearance. We reported a 40-year-old woman who had a 10-year history of an atrophic dermatofibrosarcoma protuberans. Molecular analysis showed a fusion between COL1A1 exon 31 to exon 2 of PDGFB. The lesion was totally excised, with negative margins of the resection demonstrated by CD34 immunostaining. To our knowledge, this is the second case of atrophic dermatofibrosarcoma protuberans confirmed by detection of COL1A1-PDGFB fusion gene. This appears to be the first report of a fusion between COL1A1 exon 31 to exon 2 of PDGFB in atrophic dermatofibrosarcoma protuberans. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1249657688795311.

Primary intrathoracic dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is defined as a low-grade sarcoma derived from an uncertain cell of origin in the reticular dermis. We report a fibrosarcomatous variant of DFSP (FS-DFSP) that arose primarily in the deep thoracic soft tissue. The patient was a 9-year-old girl who presented with dyspnea and low-grade fevers without a clinically detectable mass or a history of skin lesion. Imaging studies revealed a 10-cm mass entirely confined within the thoracic cavity. Three years after a marginal excision with adjuvant chemotherapy and radiotherapy, the tumor recurred in the paraspinal region. Histologically, the primary and recurrent tumors comprised a high-grade spindle cell sarcoma, with a small component of storiform, low-grade, CD34-positive spindle cells, classic for an ordinary DFSP. The diagnosis of FS-DFSP was confirmed molecularly by the demonstration of a COL1A1-PDGFB fusion by fluorescence in situ hybridization and reverse transcription-polymerase chain reaction analyses. To our knowledge, this is the first documented case of a genetically confirmed deep-seated DFSP without an associated superficial soft tissue or dermal component. The implication of this case on expanding the clinical spectrum of DFSP will have to be elucidated in future studies by applying molecular pathologic tools in deep-seated sarcomas in the proper morphologic context.