Case 1 History
The patient is a 55-year-old male with a brown papule on the left lower leg.
Histopathology
Microscopic sections show irregular pigmented epidermal hyperplasia with flattening of rete ( Fig. 14.1 ). In the dermis, there is a population of spindled and stellate cells in collagenous stroma. Cellular density varies. Peripherally, spindled cells are insinuated between coarse reticular dermal collagen bundles. Peripheral keloidal collagen bundles are sometimes informally termed collagen balls .
Diagnosis
Dermatofibroma
Clinical Presentation
Dermatofibromas present as papules or nodules. Occasionally, the appearance can be hyperpigmented. Many show central dimpling when squeezed. This is a consequence of the periphery of the tumor being tethered to adjacent reticular dermal collagen. In the clinic, dermatofibromas may mimic melanocytic nevi or cysts.
Histopathology
Microscopically, the spectrum of dermatofibroma is broad. A key scanning magnification pattern includes epidermal hyperplasia above a dermal spindle cell population. Collagen bundles are often coarsened, especially peripherally. Subcutaneous extension tends to be limited, although rarely a dermatofibroma can present wholly in the subcutis. (The designation fibrous histiocytoma may be used in this context.) There are numerous dermatofibroma subtypes based on cellular arrangement (palisaded dermatofibroma), cytoplasmic changes (lipidized or epithelioid dermatofibroma), associated stromal changes (siderotic dermatofibroma), or associated manifestations of induction (dermatofibroma with follicular germinative induction). The histomorphologic spectrum is truly diverse.
The immunophenotype of dermatofibroma is not specific. Notably, there is typically a lack of CD34 expression. The epithelioid subtype of dermatofibroma often expresses factor XIIIa, but in conventional dermatofibroma, factor XIIIa expression is often limited to dendritic cells. Epithelioid dermatofibroma also differs from conventional dermatofibroma in that it is commonly initiated by ALK rearrangement. ALK immunostaining can be used to screen for gene fusion.
Differential Diagnosis
The differential diagnosis includes neurofibroma, spindle cell melanocytic nevus (blue nevus), and scar ( Table 14.1 ).
| Dermatofibroma | Neurofibroma | Blue Nevus | Scar | |
|---|---|---|---|---|
| Epidermis | Epidermal hyperplasia (induction) | No changes | No changes | Effacement of rete, commonly |
| Classic features | Nodular population of spindled cells with coarse collagen | Wavy, spindled cells in loose myxoid stroma | Fusiform melanocytes in sclerotic stroma | Hatchwork pattern with collagen bundles and vessels arrayed perpendicularly |
| Immunohistochemistry | CD34 negative | SOX10, S100, and CD34 all positive | SOX10, Melan-A, and HMB-45 all positive | Negative |
Neurofibroma
Clinical Presentation
Neurofibroma presents as a skin-colored papule. They may occur in isolation or in multiplicity, which rarely indicates syndromic etiology.
Histopathology
Microscopy reveals a proliferation consisting of spindled or wavy fusiform cells (see Fig. 14.1 ). The cell population is often heterogenous, as it includes Schwann cells, endoneurial fibroblasts, and perineurial cells. The surrounding matrix often exhibits a fibrillar quality and includes collagen fibers, mucin, and scattered mast cells. With respect to immunohistochemistry, neurofibromas express SOX10 and S100 protein (expression is attributable to the presence of a Schwann cell component).
Blue Nevus
Clinical Presentation
Blue nevi commonly present in papular fashion. Blue nevi may be pigmented or nonpigmented. When pigmentation is absent or inconspicuous, terms such as amelanotic blue nevus or hypomelanotic blue nevus may be used.
Histopathology
Microscopic analysis reveals spindled melanocytes with variable cytoplasmic pigmentation, which may be a clue to the diagnosis ( Fig. 14.2 ). Cytologic atypicality is typically absent. Immunostaining for SOX10, HMB-45, or Melan-A may be helpful to confirm melanocytic lineage, particularly in cases lacking pigmentation.
Scar
Clinical Presentation
Scars commonly present as pale or whitish firm plaques or nodules. Scarring can occasionally present in spontaneous fashion, meaning that the patient may be unaware that a focus of scarring was precipitated by a prior injury.
Histopathology
Microscopically, a scar consists of altered collagen mixed with fibrocytes and blood vessels ( Fig. 14.3 ). The collagen is often oriented parallel to an attenuated epidermis. Vessels are commonly oriented perpendicular to the epidermis. Associated inflammation is common. Keloidal scars include markedly thickened eosinophilic collagen bundles. Immunohistochemistry is not typically used in the evaluation of a scar. Elastic tissue staining can be useful in the microscopic analysis of scarring.
Case 2 History
A 32-year-old female presents with a slowly enlarging, multinodular skin-colored plaque on her trunk.
Microscopic Findings
Sections show a hypercellular proliferation of spindled cells with a storiform pattern involving the dermis and subcutis ( Fig. 14.4 ). Cytologic atypia is not prominent. In the subcutis, spindled cells encompass individual or grouped adipocytes, which is referred to as fat trapping . Immunostaining for CD34 shows strong diffuse positivity.
Diagnosis
Dermatofibrosarcoma Protuberans
Clinical Presentation
Dermatofibrosarcoma protuberans (DFSP) may involve any site but most commonly presents with truncal involvement. DFSP typically presents as a slow-growing plaque, and diagnosis may be delayed because of the indolence of the clinical presentation. Most examples present in adulthood, but pediatric or congenital presentations of DFSP are not rare.
Histopathology
DFSP shows an infiltrative configuration involving the dermis and subcutis. The tumor cells are arrayed in a random cartwheel configuration that is often termed storiform . Infiltration of the subcutis eventuates with trapping of lipocytes. Pigmented and myxoid variants have been described. In pigmented DFSP, the tumor proper is nonpigmented but is heavily colonized by pigmented dendritic melanocytes. In myxoid DFSP, ample mucopolysaccharide is present in association with tumor cells.
Although DFSP represents an indolent, slow-growing tumor, some examples progress to include a poorly differentiated fibrosarcoma component. Although conventional DFSP holds no metastatic potential, fibrosarcomatous change with an associated increase in the mitotic index in a DFSP portends low risk for secondary spread.
With respect to immunohistochemistry, DFSP shows strong diffuse CD34 expression. Additional immunohistochemistry can be used as needed to exclude other considerations from the differential diagnosis. DFSP shows a common translocation t(17;22) (q22;q13), which results in fusion of the COL1A1 – PDGFB genes. Targeted molecular assessment (typically by fluorescence in situ hybridization for this fusion) can be used as an additional diagnostic tool.
Differential Diagnosis
Differential diagnostic considerations include dermatofibroma (see earlier and Fig. 14.4 ) and atypical fibroxanthoma (AFX) ( Table 14.2 ).
