Cellular Dermatofibroma: Clinical Overview and Prognosis

Cellular dermatofibroma is a benign skin tumor with increased cellularity compared to common dermatofibromas, sometimes complicating diagnosis. While typically non-aggressive, its histological features can resemble malignant lesions, requiring careful evaluation to prevent misdiagnosis and unnecessary treatment.

Understanding its clinical behavior, molecular characteristics, and prognosis is essential for accurate diagnosis and management.

Clinical Presentation

Cellular dermatofibroma appears as a firm, slow-growing dermal nodule, most commonly on the lower extremities, though it can also develop on the upper limbs and trunk. The lesion is usually well-circumscribed, measuring between 0.5 and 2 cm in diameter, though larger cases have been reported. Unlike conventional dermatofibromas, which often show a central dimple upon lateral compression (Fitzpatrick’s sign), the cellular subtype may be more protuberant or dome-shaped, sometimes leading to suspicion of a more aggressive neoplasm. The overlying epidermis may display hyperpigmentation or mild atrophy, particularly in long-standing lesions.

Most patients report an asymptomatic lesion, though pruritus or tenderness can occur, particularly if subjected to repeated trauma. The lesion’s color ranges from flesh-toned to reddish-brown, with some cases appearing violaceous, especially in individuals with darker skin. Unlike malignant cutaneous tumors, cellular dermatofibromas rarely ulcerate or bleed spontaneously, though superficial erosion may result from chronic irritation. Dermoscopic evaluation often reveals a peripheral pigment network with a central white scar-like area, a pattern aiding differentiation from melanocytic lesions. However, increased cellularity may obscure these features, necessitating histopathological assessment.

Palpation reveals a firm, non-fluctuant consistency, distinguishing it from cystic or lipomatous lesions. While most cases are solitary, multiple lesions have been reported, particularly in immunocompromised individuals. Growth is generally slow, though some lesions may enlarge more rapidly than conventional dermatofibromas, occasionally raising concerns for dermatofibrosarcoma protuberans (DFSP) or other spindle cell neoplasms. This underscores the importance of thorough clinical and histological evaluation.

Histopathological Characteristics

Cellular dermatofibroma exhibits increased spindle cell density within the dermis. Unlike the classic variant, which has a more collagenized stroma with interspersed fibroblasts, the cellular subtype consists of tightly packed spindle-shaped cells arranged in intersecting fascicles or storiform patterns. These cells have elongated nuclei with minimal pleomorphism and low mitotic activity, though occasional mitotic figures may be present. Atypical mitoses are absent, helping distinguish it from malignant spindle cell neoplasms.

The tumor extends into the deep reticular dermis and may involve the subcutaneous fat, displaying an infiltrative yet well-demarcated growth pattern. Entrapment of adipocytes at the periphery can occur but lacks the diffuse honeycomb infiltration seen in DFSP. Overlying epidermal changes, including basal layer hyperpigmentation and mild acanthosis, contribute to the clinical pigmentation seen in some cases. A Grenz zone—a narrow band of uninvolved papillary dermis separating the lesion from the epidermis—may be present, aiding differentiation from other fibrohistiocytic proliferations.

Collagen deposition varies, with some areas exhibiting dense sclerosis while others maintain a more myxoid matrix. Hemosiderin-laden macrophages and multinucleated giant cells are common and can mimic other histiocytic tumors. Foam cells may appear in older lesions, reflecting degenerative changes. Perivascular lymphocytic infiltrates are often mild, lacking the pronounced inflammatory response seen in certain reactive fibrous proliferations.

Immunohistochemical staining aids diagnosis, with tumor cells showing strong positivity for factor XIIIa, a marker associated with dermal dendrocytes. In contrast, CD34, typically expressed in DFSP, is negative or only focally positive. Smooth muscle actin (SMA) may show variable expression, reflecting myofibroblastic differentiation in some cases. S100 and desmin are consistently negative, ruling out neural and muscular neoplasms.

Associated Molecular Changes

Cellular dermatofibroma lacks the COL1A1-PDGFB fusion gene found in DFSP, reinforcing its benign nature. Comparative genomic hybridization (CGH) analyses have occasionally identified focal chromosomal gains or losses, suggesting some genetic heterogeneity.

Gene expression studies indicate upregulation of pathways related to fibroblast proliferation and extracellular matrix remodeling, particularly involving TGF-β signaling. This aligns with the observed increased cellularity and collagen deposition. Immunohistochemical studies show overexpression of phosphorylated ERK (p-ERK), suggesting MAPK pathway activation, though without the BRAF or NRAS mutations seen in melanocytic tumors.

Epigenetic modifications may contribute to its pathogenesis. Methylation profiling has identified distinct DNA methylation patterns compared to conventional dermatofibromas, particularly in genes regulating cell adhesion and mesenchymal differentiation. This may explain its more infiltrative growth pattern and occasional adipocyte entrapment. Alterations in non-coding RNA expression, including microRNAs involved in fibroblast proliferation, have also been reported, though their significance remains under investigation.

Differential Diagnosis

Distinguishing cellular dermatofibroma from other cutaneous spindle cell neoplasms can be challenging due to overlapping features. One key differential is dermatofibrosarcoma protuberans (DFSP), a locally aggressive tumor with a similar spindle cell proliferation pattern. DFSP typically exhibits diffuse CD34 positivity and characteristic honeycomb infiltration of subcutaneous fat, which are absent in cellular dermatofibroma. Cellular dermatofibroma shows strong factor XIIIa staining and lacks the COL1A1-PDGFB gene fusion, providing useful molecular and immunohistochemical distinctions.

Scar-like fibrous histiocytomas can mimic cellular dermatofibroma but often have more prominent sclerosis and lower mitotic activity. Superficial leiomyosarcomas, arising from smooth muscle cells, may also be considered when mitotic figures are present. However, leiomyosarcomas display cytologic atypia, nuclear pleomorphism, and desmin positivity, features not seen in cellular dermatofibroma. Spindle cell melanomas, though rare, must also be excluded, particularly in pigmented lesions. These melanomas typically exhibit S100 and SOX10 positivity, markers absent in dermatofibromas.

Possible Therapies

Surgical excision is the primary treatment, given the lesion’s benign nature and low recurrence risk. Unlike aggressive spindle cell tumors requiring wide excision, cellular dermatofibromas can typically be removed with a simple elliptical excision with narrow margins. Histological evaluation post-excision confirms complete removal and rules out malignancy. While shave excision or punch biopsy may be used for diagnosis, they are not recommended as definitive treatment due to the risk of persistence or regrowth.

For patients seeking non-surgical options, intralesional corticosteroid injections have been explored to reduce lesion size and alleviate symptoms such as pruritus or tenderness, though this approach is not widely used. Laser therapies, including pulsed dye laser and CO2 laser ablation, have been employed for cosmetic improvement when pigmentation is a concern. While these methods can enhance aesthetic outcomes, they do not eliminate the lesion histologically and may require multiple sessions. Long-term follow-up is generally unnecessary unless diagnostic uncertainty or recurrence arises.

Prognostic Considerations

The prognosis for cellular dermatofibroma is excellent, with an extremely low risk of malignant transformation or aggressive behavior. Unlike DFSP, which is locally invasive and has a high recurrence rate, cellular dermatofibroma rarely recurs after complete excision. When recurrences occur, they result from incomplete removal rather than intrinsic tumor aggressiveness. In such cases, re-excision is curative, with no need for additional therapy.

Histological features such as increased mitotic activity or deep extension into subcutaneous fat may raise concerns, but studies have not shown a correlation between these findings and adverse outcomes. Immunohistochemical markers and molecular analyses further support its benign classification, with no evidence of mutations or translocations linked to malignancy. Longitudinal studies consistently report stable clinical courses, reinforcing its classification as a benign fibrohistiocytic proliferation.