Benign Fibrous Histiocytoma (BFH), also known as dermatofibroma, is a common mesenchymal tumor of the skin. BFH is a benign tumor arising from fibroblasts and histiocytes affecting the dermis and subcutaneous soft tissues (1). It typically presents as an isolated cutaneous nodule that is firm or cystic, skin-colored or brown, later developing into a polypoid nodule or raised plaque (2). BFH primarily affects adults and is frequently found on the extremities (3–5). There are multiple pathological subtypes of BFH, including the classic dermal FH, as well as cellular, aneurysmal, and atypical variants. Metastasis of BFH is extremely rare, with only a few reports documented in the literature (2, 5–9). This paper summarizes 10 cases of metastatic BFH diagnosed at Fudan University Shanghai Cancer Center from 2009 to 2024, with detailed reports on three cases. In this article, we use BFH as an umbrella term that includes the conventional cutaneous form and a range of histologic variants. These variants comprise cellular, aneurysmal, and atypical forms, as well as less common lipidized, palisaded, and myxoid patterns. By low-grade malignant fibrohistiocytic tumors, we refer specifically to atypical fibroxanthoma (AFX) under contemporary criteria, which is classified as BFH in this study.

Among the ten cases reviewed, three were classified as cellular variants, and one as a hemangioma variant. The primary tumor sites included two cases in the head and neck, four in the limbs, one in the chest wall, one in the shoulder, one in the testis, and one with an unknown origin. Metastatic patterns included five cases with pulmonary metastases, five with lymph node metastases, two with subcutaneous metastases, and one with pleural metastasis (Table 1).

BFH is primarily composed of fibroblasts and histiocytes, exhibiting benign yet diverse histological features (2, 6). Common variants include cellular, aneurysmal, and atypical forms, along with less frequent variants such as lipidized, palisaded, and myxoid types (6). These subtypes differ in pathology and prognosis. For example, cellular FH is characterized by larger cells, higher density, and less intercellular collagen, whereas atypical FH displays a mixture of pleomorphic spindle and polygonal cells with multinucleated giant cells, prominent nucleoli, and hemosiderin deposits (10, 11). Immunohistochemistry aids in the differentiation and diagnosis of BFH from other benign lesions, such as neurofibromas, leiomyomas, amelanotic melanomas, and dermatofibrosarcoma protuberans (DFSP). DFSP typically exhibits high CD34 expression, while BFH is often CD34-negative (2, 6, 12–14). Smooth muscle actin (SMA) is a marker for smooth muscle tumors and is generally negative in BFH but positive in leiomyomas (15). Amelanotic melanomas often show diffuse S-100 positivity, whereas BFH is S100 negative (2). In our cases, immunohistochemical analyses of both primary and metastatic lesions were performed to confirm tumor type and metastasis. Diagnostic markers used included Vimentin, S100, SMA, CD34, CD68, CD163, Desmin, AE1/AE3, and Ki67. AE1/AE3 serves as an epithelial tumor marker, Vimentin identifies fibroblasts, CD68 highlights monocytes, histiocytes, osteoclasts, mast cells, and giant cells, and Desmin is specific for skeletal muscle tumors. Beyond morphology and immunophenotype, recent studies point to several molecular clues related to metastasis. In general, metastasizing BFH carries a higher burden of copy-number alterations, most often gains of chromosome 7 and 8q and loss of Xq (10). PKC-related gene fusions such as CD63::PRKCD have also been documented, particularly in aneurysmal lesions, and metastasizing specimens may display recurrent gains of chromosomes 1, 3, 8, and 11 (16).

BFH predominantly occurs in the extremities of middle-aged adults, although it can develop in any anatomical site and at any age. Different subtypes share similar predilection sites and age ranges (2, 11, 17). Recurrence risks vary by subtype. Conventional FH and most variants rarely recur even with incomplete excision (1-2%). However, cellular, aneurysmal, and atypical BFH have recurrence rates as high as 20% (10, 11, 17, 18). Metastasis of BFH is exceedingly rare, and most cases reported involve the lungs and lymph nodes. Although histological features associated with recurrence and metastasis include larger size, aneurysmal changes, high cellularity, pleomorphism, high mitotic rates, and necrosis (6), subsequent studies suggest that morphology alone cannot reliably predict aggressive behavior (5, 10). Studies indicate that recurrent or large-cell variants of FH are more prone to metastasis (5). Among the three patients detailed in this study, all exhibited BFH metastasis and multiple recurrences. One case involved a rare occipital primary BFH with submental and pulmonary metastases, later progressing to widespread soft tissue metastases. The other two cases demonstrated lymph node metastases, with one patient also exhibiting subcutaneous metastasis. These patterns of metastasis are clinically uncommon.

Surgical excision remains the primary treatment for BFH. Most patients achieve a cure through surgery. However, when tumor location or disease burden makes resection infeasible or unacceptably morbid, radiotherapy or systemic therapy should be considered in consultation with a multidisciplinary team. In the absence of formal guidelines for radiotherapy or chemotherapy in BFH, management is typically extrapolated from other soft-tissue tumors. To date, these modalities have not shown clear efficacy. A case report described a patient with aneurysmal-type FH and metastasis who could not undergo surgery due to tumor vascularity and disease severity (19). This patient received palliative radiotherapy and chemotherapy without success, ultimately succumbing to the disease. Another patient with pulmonary metastases received chemotherapy, starting with ifosfamide and then single-agent doxorubicin (20). The disease progressed despite both treatments. One case series reported five patients who received chemotherapy and five who received radiotherapy (5). Chemotherapy regimens included doxorubicin–ifosfamide, sorafenib, and gemcitabine. Four of the five patients experienced disease progression. Among those treated with radiotherapy, one patient died. Thus, disease-specific radiotherapy protocols and effective systemic therapies for BFH remain undefined, highlighting the need for therapeutic development and prospective evaluation.

Compared with prior publications—most of which are single-case reports or very small series (2, 4, 6, 8, 21)—our study offers several advantages. First, we report a single-center cohort of 10 patients collected over 15 years with uniform pathology review, enhancing internal comparability. Second, all cases are previously unreported. Third, we expand the clinicopathologic spectrum by documenting uncommon presentations and atypical metastatic patterns, notably multifocal subcutaneous deposits. Fourth, we integrate radiologic and pathologic assessment and apply a pragmatic immunohistochemical framework to both primary and metastatic lesions, helping to reduce misclassification between BFH and other soft-tissue tumors. Fifth, we report real-world experience with multimodal combined therapy, including various permutations of surgery, radiotherapy, and chemotherapy. Using patient-level timelines, we delineate recurrence windows and initial metastatic sites. These observations inform treatment strategies for patients with metastatic BFH. Such integrated information is rarely consolidated in prior reports. Finally, we propose core data elements for standardized reporting to facilitate cross-study comparisons and future registry-based aggregation. Taken together, these features make our series a more informative, practice-oriented reference than the existing literature on metastatic BFH.