Non-melanocytic Skin Tumors
Moderator: Dr. Philip E. LeBoit
Section 4 -
FIBROHISTIOCYTIC TUMORS OF SKIN
Jennifer M. McNiff, M.D.
Yale University School of Medicine
Dermatofibroma (Fibrous Histiocytoma):
Typically firm papule on extremities of young adults, may be pigmented
Case 4-1: Classic dermatofibroma
A 35-year-old woman presented with a firm papule on her thigh.
Case 4-1 - Slide 1
Case 4-2: Atrophic dermatofibroma
A 40-year-old man had a small papule on his shoulder.
Case 4-2 - Slide 1
Case 4-3: Aneurysmal dermatofibroma (sclerosing hemangioma)
A 42-year-old man had a discolored firm nodule on his proximal thigh.
Case 4-3 - Slide 1
Case 4-4: Deep dermatofibroma
A 36-year-old man had a firm nodule on his back, with a clinical impression of cyst.
Case 4-4 - Slide 1
Case 4-5: Granular dermatofibroma
A 30-year-old man had a nodule on his back, with a clinical impression of scar.
Case 4-5 - Slide 1
Case 4-6: Sclerotic fibroma
A 50-year-old woman had a nodule on her abdomen with a clinical impression of nevus.
Case 4-6 - Slide 1
- Proliferation of fibroblasts centered in
mid-dermis with storiform growth pattern
- Spindle cells trap dense collagen into
- Cells are plump with angular nuclei, mitoses may be present
- Epidermal hyperplasia common, sometimes with follicular or sebaceous induction
Histologic variants presenting diagnostic challenges:
- Deep DF
- Granular cell
- Angiomatoid DF
- DF with atypical cells (Atypical
cutaneous fibrous histiocytoma)
- Seen in Cowden's disease (multiple hamartoma
syndrome) or sporadically
- Small pearly papules or nodules, any site
- Well-circumscribed hypocellular bundles of
- Collagen lies in parallel arrays, separated by spaces containing mucin
(plywood grain pattern)
- IP staining +CD34, actin, vimentin
Epithelioid Cell Histiocytoma
Typically polypoid lesions, most common on extremities of
adults. Clinical impression often includes pyogenic granuloma, nevus, and basal cell carcinoma.
Case 4-7: Epithelioid cell histiocytoma
A 40-year-old man presented with an exophytic nodule on his foot, with a clinical impression of basal cell carcinoma.
Case 4-7 - Slide 1
- Polypoid and centered in papillary
dermis, usually with epidermal collarette
- Epidermis flattened with effaced rete
- Even distribution of large angular
epithelioid cells which tend to interdigitate
- Abundant eosinophilic cytoplasm,
large eccentrically placed nuclei
- Minor component of spindle cells,
abundant small blood vessels
- IP staining positive for factor
XIIIa, vimentin, negative for S100, HMB45, CD34
- Desmoplastic (dermal) Spitz nevus:
nested, not interdigitating cells, S100 positive
- Malignant melanoma: cellular atypia,
epidermal involvement, S100 positive
- Histiocytoid hemangioma: enlarged
endothelial cells, CD31 positive
- Reticulohistiocytoma: more abundant
cytoplasm, secondary elements
- Atypical fibroxanthoma: more atypia,
abnormal mitoses, sun-damaged skin of elderly
This unique variant of benign fibrous histiocytoma was first recognized in 1988, and
represents approximately 0.5% of benign fibrous histiocytomas. Unlike classic dermatofibroma, however,
most cases of epithelioid cell histiocytoma (ECH) are lesions of papillary dermis, with uniform
epithelioid cells, sharp circumscription, and prominent vascularity. Intranuclear inclusions are
frequently identified, so that the cells of ECH may easily be mistaken for spitzoid melanocytes. Focal
clusters of S100 positive cells may also be seen in ECH, and represent a diagnostic pitfall. In
addition, the clinical presentation and prominent vessels create the impression of a primary vascular
neoplasm. ECH merits recognition because of its unusual and potentially confounding histologic features.
- Young adults with 1-2 cm asymptomatic plaques
- Favors shoulder area, axilla, upper arm, and neck
Case 4-8: Dermatomyofibroma
A 32-year-old woman presented with a plaque on her arm, with a clinical impression of dermatofibroma versus mastocytoma.
Case 4-8 - Slide 1
- Uniform spindle cells in mid to deep reticular dermis and
- Fascicles lie parallel to epidermis
- Distinctive sparing of adnexal structures
- IP MSA +, SMA -, desmin -, CD34 –
This represents a unique fibrocytic lesion described first as plaque-like dermal
fibromatosis in 1991 by Hugel, and subsequently as dermatomyofibroma by Kamino in 1992.
Multinucleate Cell Angiohistiocytoma
- Multiple dome-shaped or flat papules 2-15 mm in
- Tendency to be clustered on an anatomic area, but may be
- Most often located on dorsal hand and thigh, also reported on face
- Age range 35 to 74 years, mean 56 years
- Lesions usually present for years, occasional reports of spontaneous regression
Case 4-9: Multinucleate cell angiohistiocytoma
A 59-year-old woman presented with a flat papule on the extensor surface of her middle finger.
Case 4-9 - Slide 1
- Increased vessels in a diffuse pattern centered
in the upper reticular dermis
- Scattered multinucleate cells with 3-10 nuclei and
scalloped angular cytoplasm
- Slightly coarse collagen, vaguely parallel to
- Sparse perivascular lymphocytic infiltrate
"collagen balls" or trapping of collagen at the periphery
Some observers view multinucleate cell angiohistiocytoma as a variant of dermatofibroma,
but the consistent presence of multiple lesions, especially on hands, and the absence of follicular
induction or "collagen balls" suggest these lesions represent a unique entity.
Cellular Digital Fibroma
Present as innocuous papules on fingers, toes
Case 4-10: Cellular digital fibroma
A 34-year-old woman developed a small firm round papule on her finger, with a clinical impression of wart.
Case 4-10 - Slide 1
- Dome-shaped papule covered by normal squamous
- Intersecting fascicles of delicate spindle cells fill the superficial
- Stroma is fibrotic or occasionally myxoid
- Inflammation is typically absent
- Spindle cells label strongly
for CD34, with few scattered Factor XIIIa positive stromal cells, and no labelling for S100 protein or
- May show a resemblance to dermatofibrosarcoma protuberans (DFSP)
Cellular digital fibromas represent a recently described variant of benign acral fibromas with strong
CD34 positivity. There is a growing list of CD34-positive tumors in the literature, including sclerotic
fibroma, solitary fibrous tumor, pleomorphic fibroma, DFSP, and vascular lesions. The clinicopathologic
features of cellular digital fibromas seem unique among this list, however. Importantly, superficial
biopsies showing a high degree of cellularity and storiform growth may raise diagnostic concern regarding
DFSP. DFSP is rare on the digits of adults, however, and cellular digital fibromas are typically small
and clinically innocuous. Nonetheless, awareness of cellular digital fibroma is important to prevent
misdiagnosis and over treatment of these small benign tumors.
- Rapidly growing self-limited nodules, range
from 1-5 cm
- Sometimes tender; typically affect young to mid-age adults
- "Pseudosarcomatous" proliferation of spindle
cells in myxoid stroma
- Tissue culture appearance
- Mitoses may be numerous, edema and extravasated RBCs common
Fibrosarcoma and malignant fibrous histiocytoma
Fibrous Hamartoma of Infancy
- Typically develops in first two years of
- Small rapidly growing nodule of subcutis or deep dermis.
- About one quarter may be present at birth
- More common in boys
- Axillae and inguinal regions often affected, uncommon on hands and
- Often several centimeters in diameter
Case 4-11: Fibrous hamartoma of infancy
A one-year-old girl presented with a 3-centimeter plaque on her lower abdomen, with a clinical impression of dermatofibrosarcoma protuberans.
Case 4-11 - Slide 1
- Three distinct components giving an "organoid
- Trabeculae of spindle
cells and collagen
- Loose round areas with basophilic mucoid matrix
- Variable amounts of mature fat, often abundant
spindle cell areas may stain for actin
- Loose myxoid areas stain for mucin
- Infantile fibromatosis (usually more deeply
situated, lacks "organoid pattern"
- Myofibromatosis (often multinodular,
- Calcifying aponeurotic fibroma (acral, older
- Giant cell fibroblastoma (more widespread myxoid areas, giant
Fibrous hamartoma of infancy has a very characteristic pattern when all three tissue
components are present. In more fibrous examples, this lesion maybe confused with other fibrous tumors
of childhood. Distinction is important because this is a benign lesion, cured by local excision. There
is a low but definite rate of recurrence, estimated to be about 16%, but recurrences are indolent and
cured by excision. The nature of the cells, in particular the myxoid organoid areas, remains obscure.
Infantile Digital Fibroma
- Firm nontender nodule less than 2 cm in
- Usually present within first year of life, one-third present at
- Fingers affected more frequently than toes, thumb and great toes
- Lesions may be multiple, affecting more than one digit on same
- Local recurrence is common, seen in > 60% cases
Case 4-12: Infatile digital fibroma
A 9-month-old boy presented with two nodules on his right ring finger.
Case 4-12 - Slide 1
Key histologic features:
- Nodular aggregates of spindle cells, sometimes trapping adnexa
- Characteristic small round perinuclear inclusions in cytoplasm of fibroblasts
- Inclusions are eosinophilic and resemble erythrocytes
- Inclusions are red by Masson Trichrome, purple by PTAH, and do not stain by PAS or Alcian blue
- Acquired digital fibrokeratoma
- Palmar fibromatosis
- Infantile myofibromatosis
The inclusion bodies in this lesion are diagnostic, and have
led to the alternate name "inclusion body fibromatosis." Although there is an initial period of growth
in these tumors, many tend to regress spontaneously if followed over time. There is a recent report of
treating infantile digital fibroma successfully with intralesional fluorouracil rather than with
surgery. The lesions are thought to derive from myofibroblasts, and the inclusions are suspected to
contain bundles of actin myofilaments. There may be a relationship to trauma in some cases, and
histologically similar lesions have been reported in adults following trauma in other sites.
- Nearly always on sun-exposed skin of elderly
- Rapid growth, ulcerated surface
- Subset may be seen on extremities of younger patients
Case 4-13: Atypical fibroxanthoma
A 79-year-old woman presented with an eroded papule on her cheek, with a clinical impression of squamous cell carcinoma.
Case 4-13 - Slide 1
- Dome-shaped nodule
- Pleomorphic cells, some spindled, some bizarre shapes
- Numerous mitoses, including atypical forms
- Prominent solar elastosis
- IP: Procollagen +, MSA +, CD34 -, S100 protein -
- Spindle squamous cell carcinoma
- Malignant melanoma
- Pleomorphic fibroma
- Atypical dermatofibroma
- Slow growing tumor, trunk proximal extremities, young and middle-aged adults
- Solitary or multiple nodules within indurated plaque, sometimes atrophic
- Usually greater than one cm in diameter
- Local recurrence common, distant metastasis rare
Case 4-14: Dermatofibrosarcoma
A 65-year-old woman presented with a 2-centimeter plaque on her left flank.
Case 4-14 - Slide 1
- Dermal and subcutaneous tumor
- Bland spindle cells form storiform patterns
- Honeycomb pattern of spindle cells in subcutaneous fat
- Minimal intermingled mature collagen
- Epidermis spared, usually not hyperplastic
- May show fibrosarcomatous areas
- Deep dermatofibroma
- Malignant fibrous histiocytoma
- Diffuse neurofibroma
The distinction between dermatofibroma (DF) and
dermatofibrosarcoma protuberans (DFSP) continues to pose diagnostic dilemmas for pathologists in daily
practice. With routine histology, DFSP tends to be more deeply situated and invades the subcutis in a
more diffuse manner. Although some DFs invade the subcutis, this is usually present as tapered
aggregates of cells resembling the limbs of starfish. Also, DFs tend to contain abundant mature keloidal
collagen and be associated with epidermal hyperplasia, features not typical of DFSP.
By immunohistochemistry, most DFSP stain diffusely for CD34, while DF typically stain for
Factor XIIIa and not CD34. However, some DF stain at least focally for CD34, and there are reports of
"indeterminate fibrohistiocytic lesions" with overlapping features of DF and DFSP.
DFSP is characterized by a specific cytogenetic translocation, t(17;22)(q22;q13) and a supernumerary
ring chromosome derived from translocation of t(17;22). These translocations affect genes related to the
formation of collagen type 1 and platelet-derived growth factor.
Giant Cell Fibroblastoma
- GCF presents as a slowly growing painless mass, most
common in childhood
- Recent reports describe cases of DFSP with areas of GCF
and vice versa, as well as GCF recurring as DFSP years after initial excision
- GCF is now generally regarded as a variant of DFSP
Case 4-15: Giant cell fibroblastoma/DFSP
A 13-year-old girl presented with a 3-centimeter multinodular tumor in her groin.
Case 4-15 - Slide 1
Key histopathologic findings:
- GCF shows bland spindle cells and multinucleate giant
cells in a myxoid stroma
- Sinusoidal spaces resembling vessels are characteristic
- GCF stain for CD34 and vimentin
- Malignant fibrous histiocytoma
- Myxoid liposarcoma
Despite the histologic differences between GCF and DFSP, a biologic similarity between the
lesions is supported by the coexistence of both tumors in one site, the positive staining of both with
CD34, and recent cytogenetic evidence of rearrangement of chromosomes 17 and 22 in both GCF and DFSP.
- Haycox CL et al. Immunohistochemical characterization of dermatofibrosarcoma protuberans with practical applications for diagnosis and treatment. J Am Acad Dermatol 1997;37:438-444.
- Kamino H, Jacobson M. Dermatofibroma extending into the subcutaneous Tissue: Differential diagnosis with dermatofibrosarcoma protuberans. Am J Surg Pathol 1990;14:1156-1164.
- Kaddu S, McMenamin ME, Fletcher CDM. Atypical fibrous histiocytoma of the skin. Clinicopathologic analysis of 59 cases with evidence of infrequent metastasis. Am J Dermatopathol 2002;26:35-46.
- Glusac EJ, McNiff JM. Epithelioid cell histiocytoma: a simulant of vascular and melanocytic neoplasms. Am J Dermatopathol 1999;21:1-7.
- Kamino H, Reddy VB, Gero M, et al: Dermatomyofibroma: A cutaneous plaque-like proliferation of fibroblasts and myofibroblasts. J Cutan Pathol 1992;19:85-93.
- Shapiro PE, Nova MP, Rosmarin LA, Halperin AJ. Multinucleate cell angiohistiocytoma: A distinct entity diagnosable by clinical and histologic features. J Am Acad Dermatol 1994;30:417-422.
- McNiff JM, Subtil A, Cowper SE, Lazova R, Clusac EJ. Cellular digital fibromas: distinctive CD34-positive lesions that may mimic dermatofibrosarcoma protuberans. J Cutan Pathol 2005:32:413-418.
- Dickey GE et al. Fibrous hamartoma of infancy: current review. Pediatr Dev Pathol 1999;2:236.
- Hayashi T et al. Infantile digital fibromatosis: a study of the development and regression of cytoplasmic inclusion bodies. Mod Pathol 1995;8:548.
- Cin PD et al. Cytogenetic and immunohistochemical evidence that giant cell fibroblastoma is related to dermatofibrosarcoma protuberans. Genes, Chromosomes, & Cancer 1996;15:73-75.