Plexiform Soft Tissue Tumors

INTRODUCTION

The term plexiform refers to a pattern of local infiltration in which multiple, interconnected tumor nodules ramify in adjacent stroma or normal tissues and appear discrete in cross section. Thus, plexiform lesions are not circumscribed. Many tumor types can develop a plexiform pattern, and some of these form distinct clinicopathologic subtypes. Most are benign but can recur or regrow locally, due to failure to excise all outlying branches of the lesion. In addition, plexiform fibrohistiocytic tumor has metastatic potential. The differential diagnosis is summarized in Table 22.1.

PLEXIFORM FIBROHISTIOCYTIC TUMOR

Clinical Features

Plexiform fibrohistiocytic tumor (PFHT) was first described in 1988 with 65 cases in the original report by Enzinger and Zhang.¹ Subsequent series of 14² and 22³ cases, and more recently, a further series of 66⁴ cases have confirmed the original description. PFHT is a slow-growing tumor that occurs mainly in adolescents and young adults, originally with a female predominance but with more equal sex distribution in later series. It forms a painless dermal/subcutaneous nodule, often tethered to adjacent tissues, and mostly on the upper limbs and head and neck region. One case arose in an irradiation field 7 years after treatment for malignant hemangiopericytoma.⁵

In the 2013 World Health Organization classification, PFHT is categorized as a so-called fibrohistiocytic tumor of intermediate (rarely metastasizing) biologic potential. A total of 37% of the original series of PFHT recurred, usually within 2 years, and two cases (3%) metastasized to regional lymph nodes. The overall recurrence rate is 33%, but only 2/16 (12.5%) recurred in one series of 22 patients.³ However, in this series, one case metastasized to lymph node and two additional cases metastasized to lung. One further example with apparent lymph node metastasis has been reported.⁶ There seems to be no correlation between histologic features and behavior. A case with cytologic atypia has not recurred after 10 years.⁷

TABLE 22.1 Differential Diagnosis of Plexiform Soft Tissue Tumors

	Clinical Features	Microscopic Features	Ancillary Investigations
Plexiform fibrohistiocytic tumor	Young adults, mostly upper limb, head and neck One-third recur, rare cases metastasize	Nodules based on dermal-subcutaneous junction Rounded cells, multinucleated cells, lymphocytes Some have branching bundles of fibroblasts Rarely myxoid or atypical	SMA+, CD68+, CD34−, S100 protein−
Giant cell tumor of soft parts of low malignant potential	Mostly upper limb Subcutaneous or subfascial Multinodular or circumscribed Can recur, rarely metastasizes	Uniformly distributed large osteoclast-like giant cells, bland mononuclear cells Hemorrhage, peripheral osteoid, or bone formation Vascular invasion	CD68+ in giant cells
Cellular neurothekeoma	Young adults, upper extremity, head and neck Recurrence rare, no metastases	Dermal Rounded nodules of uniform rounded cells Multinucleated cells rare Often myxoid Can show focal nuclear atypia	SMA+, NKIC3+, MITF+, S100 protein−, HMB45−
Dermal nerve sheath myxoma	Circumscribed multilobulated myxoid lesion, low cellularity	Spindle cells can show focal pleomorphism or multinucleation	S100 protein+ in myxoid areas, EMA+ at periphery of nodules
Plexiform schwannoma	Young adults, extremities, head and neck, gastrointestinal tract Deep variant mostly in females	Dermal or subcutis, rarely deeper Variably sized nodules of Schwann cells Mostly Antoni A pattern Nuclear pleomorphism can be seen, but necrosis rare Cellular variant has hypercellular fascicles, mitoses	S100 protein+, EMA+ at periphery of nodule
Plexiform neurofibroma	Associated with neurofibromatosis type 1 Can involve large nerves in deep locations or more superficial ones Can undergo malignant change Can extend extraneurally as diffuse neurofibroma	Transitions from normal nerve Nerve expanded by variable myxoid stroma and increased cellularity Atypical variant has nuclear crowding, pleomorphism Diffuse extraneural component in some	S100 protein+ focally
Diffuse neurofibroma	Some associated with neurofibromatosis type 1 Children and young adults Head and neck, subcutaneous infiltrative plaque Associated with plexiform neurofibroma—extends outside nerve bundles into soft tissue	Sheets of short spindle cells in loose fibrous stroma, infiltrating between normal structures Wagner Meissner bodies	S100 protein+ diffusely in nuclei
Plexiform xanthoma	Adult males, solitary or rarely multiple Knee, elbow Hypercholesterolemia rare	Irregularly sized nodule in dermis and subcutis Sheets of vacuolated macrophages Occasional giant cells	CD68+
Plexiform ossifying fibromyxoid tumor	Young adults, limbs, head and neck	Subcutaneous Each nodule encapsulated Glomus-like cells with small rounded nuclei and clear cytoplasm	S100 protein+, GFAP+, desmin+ focally. EP400-PHF1 fusion transcripts
Plexiform leiomyoma	Subcutaneous or female genital tract No specific clinical features	Nonencapsulated nodules without atypia, mitoses, or necrosis	SMA+, desmin+, h-caldesmon+

Pathologic Features

Most examples arise at the dermal-subcutaneous junction (Fig. 22.1) and can extend superficially or deeply (e-Fig. 22.1) but sometimes are wholly in dermis (e-Fig. 22.2). Two principal histologic patterns are described. Fortythree percent display a fibrohistiocytic picture with nodules of rounded or spindled cells with scattered osteoclast-like multinucleate giant cells, chronic inflammation, microhemorrhages, and hemosiderin (Fig. 22.2, e-Figs. 22.3 and 22.4). A total of 23% are predominantly fibroblastic with plexiform bundles of uniform spindle cells (Fig. 22.3, e-Fig. 22.5), and 34% have a mixed pattern (e-Figs. 22.6 to 22.8). Occasional pleomorphic cells are seen, and mitotic figures are described up to 7 per 10 hpf. Myxoid change, bone formation, and focal cytologic atypia⁷ are rare findings. In older lesions, the nodules are gradually replaced by fibrous tissue (e-Figs. 22.9 to 22.11).

Ancillary Investigations

Immunostaining for CD68 is positive in rounded cells (e-Fig. 22.12) and in the multinucleate giant cells, which are probably histiocytic and nonneoplastic. The spindle cells have a myofibroblastic immunophenotype with focal reactivity for SMA, and occasionally for calponin, but none for desmin or h-caldesmon. S100 protein, FXIIIa, and CD34 are negative in lesional cells. Ultrastructurally, the few reports variously indicate that the lesional cells comprise a mixture of fibroblasts, myofibroblasts, and undifferentiated mesenchymal cells.²,⁸ The findings are similar to those in other benign or malignant fibrohistiocytic tumors.

Clonal genetic abnormalities have been reported in a small number of cases, but no consistent changes have been found. One example had a complex karyotype with numerous deletions,⁹ another demonstrated a simpler karyotype of 46,XY,t(4;15)(q21;q15),¹⁰ and a third revealed a 46,X,del(X) (q13)[3]/46,XX[23] karyotype.¹¹ All cases examined have been diploid.³

FIGURE 22.1 Plexiform fibrohistiocytic tumor. The tumor comprises multiple nodules centered on dermal-subcutaneous junction and extending into both dermis and subcutis.

FIGURE 22.2 Plexiform fibrohistiocytic tumor. The fibrohistiocytic nodules are circumscribed and contain a mixture of bland histiocyte-like cells and osteoclast-like giant cells, with a sprinkling of lymphocytes.

CELLULAR NEUROTHEKEOMA

Cellular neurothekeoma has many similarities to PFHT. Indeed, in some cases, the distinction often cannot be made, and it has been proposed that the two entities are closely related if not identical, differing essentially by the plane in which they are located.¹² Cellular neurothekeoma was originally thought to be a cellular variant of nerve sheath myxoma, and the term neurothekeoma has included both entities (see Chapter 20)

Only gold members can continue reading. Log In or Register to continue