Myofibroma, Myopericytic Tumors, Myoepithelioma, and Myofibroblastoma



Myofibroma, Myopericytic Tumors, Myoepithelioma, and Myofibroblastoma





INTRODUCTION

This chapter concerns tumors that are usually benign and show predominant myofibroblastic or partial myoid differentiation. The former are distinguished from tumors composed of reactive or neoplastic myofibroblasts admixed with fibroblasts (see Chapter 3) and from low-grade and pleomorphic myofibrosarcoma (Chapters 10 and 13, respectively). Many tumors discussed in this chapter have similar or overlapping features and are terminologically similar, which can cause confusion. The features of the different cell types are summarized in Table 7.1.

Myofibroma is a tumor of myofibroblasts with morphologic features that overlap with those of pericytic neoplasms. The latter are derived from vascular pericytes that proliferate and manifest myoid or glomus cell differentiation, giving rise to hemangiopericytomatous tumors with a variety of patterns. Myoepithelioma shows, in varying degree, both myoid and epithelial differentiation. Apart from those in the genital tract (see Chapter 8), soft tissue neoplasms termed myofibroblastomas are probably composed of specialized or modified smooth muscle cells rather than myofibroblasts. The differential diagnosis is summarized in Table 7.2.


MYOFIBROMA


Clinical Features

Although predominantly a lesion of early life, including congenital incidence, myofibroma can also occur in adults.1 It can be single or multicentric, and familial forms have been described with autosomal dominant inheritance. Solitary lesions usually arise in dermis or subcutis, and occasionally skeletal muscle especially in the head and neck region (with a subset within the oral cavity2,3), and in bone, trunk, and proximal extremities. They are benign and many cases regress spontaneously, apparently




by apoptosis, although about 10% recur. Multicentric tumors are more common in females, involve bone and viscera (gastrointestinal tract, heart, lung), and can be fatal.4








TABLE 7.1 Features of Selected Spindle Cell Types

Morphology

Immunohistochemistry

Electron Microscopy


Myofibroblast

Tapered or ovoid, oval nucleus with single punctate nucleolus, variable amounts of amphophilic cytoplasm


Indistinct cell membrane

SMA+ (subplasmalemmal “tram-track” distribution), desmin±, h-caldesmon−, SMM−


Rarely CK+ (mostly in intra-abdominal lesions)

Moderate amounts of rough endoplasmic reticulum, subplasmalemmal stress fiber continuous with fibronexus fibril


No significant external lamina, junctions, or pinocytotic vesicles


Myopericyte

Short, tapered, elongated, or plump spindle cell with ovoid or tapered nucleus, moderate eosinophilic cytoplasm


Glomus cell interpreted as specialized rounded form

SMA+, h-caldesmon+, desmin+ occasionally, CD34+ rarely

Resembles smooth muscle cell: abundant cytoplasmic filaments with dense bodies, continuous external lamina, micropinocytotic vesicles


Myoepithelial cell

Usually tapered spindle cell with moderate amounts of eosinophilic cytoplasm


Can assume polygonal, clear cell, plasmacytoid, or rhabdoid form

CK+, S100 protein+, calponin+, P63+, desmin−

Intercellular junctions (desmosomes), tonofilaments, bundles of myofilaments with dense bodies


Smooth muscle cell

Nontapered (parallel-sided), abundant slightly fibrillary eosinophilic cytoplasm (also seen alongside nuclei)


Nucleus has rounded or blunt ends, paranuclear vacuole


Can assume clear cell or epithelioid form

SMA+, desmin+, h-caldesmon+, calponin+


Some express CK (dot), EMA, S100 protein

Myofilaments with dense bodies throughout cytoplasm


Continuous or interrupted (fragmented) external lamina, micropinocytotic vesicles often prominent









TABLE 7.2 Differential Diagnosis of Myofibroma, Myopericytoma, Myoepithelioma, and Myofibroblastoma

Typical Clinical Features

Microscopic Features

Ancillary Investigations


Myofibroma

Mostly in children, occasionally in adults, in head and neck, extremities, bone


Dermal or subcutaneous


Occasionally visceral and multicentric


Mostly benign but deep multicentric forms can be fatal

Circumscribed, occasionally central necrosis


Nodules of myofibroblasts, central smaller cells with pericytomatous pattern


Giant cells, ossification, intravascular spread

SMA+, desmin−, h-caldesmon−, S100 protein−, CK−


Nodular fasciitis

Young adults, extremities, head and neck


Short history (weeks); rarely up to a year


Rapid growth then stops <5 cm

Circumscribed or mildly infiltrative myofibroblastic tumor


Variably myxoid, cellular and collagenous areas


Normal mitoses acceptable but not atypia or necrosis

SMA+, desmin±, h-caldesmon−, t(17;22)(p13;q22.1), USP6-MYH9 fusion


Myopericytoma

M > F, limbs, head and neck, trunk, in dermis, or subcutis


Single or multiple


Intravascular and malignant variants occur

Circumscribed, encapsulated


Prominent pericytomatous pattern


Myoid or glomus cells around vessels or in nodules, or slender spindle cells in perivascular whorls


Malignant variants have infiltration, pleomorphism, mitoses, necrosis

SMA+, caldesmon+, desmin−, CD34−, S100 protein−, CK−, t(7;12) (p21−22;q13−15), ACTB-GLI fusion


Myoepithelial tumor/mixed tumor

Adults, limbs and girdles, rarely head and neck or trunk


Dermis, subcutis, or deep soft tissue


Malignant variants occur

Resembles salivary gland counterparts


Epithelial cords, nests, or sheets, plasmacytoid change, and rarely pure spindle cell pattern


Ductules in mixed tumor


Chondromyxoid stroma

Variable expression of S100 protein, CK, EMA, GFAP, SMA, h-caldesmon, calponin


EWSR1 rearrangement by FISH±


Mammary-type myofibroblastoma

Breast M = F


Inguinal region M > F, buttock, abdominal wall


Painless, slow-growing, rarely >6 cm diameter


Benign

Circumscribed tumor comprising irregular fascicles of spindle cells, collagenous bands, variable adipose tissue, mast cells


Resembles spindle cell lipoma


Atypical and epithelioid variants occur

CD34+, desmin+, SMA±, h-caldesmon−, S100 protein−, CK−


Intranodal myofibroblastoma

Inguinal lymph node, rarely submandibular node


Very rarely recurs

Rim of lymph node


Solid, hemorrhagic cut surface


Cellular fascicles of slender spindle cells with nuclear palisading


Extravasated erythrocytes, hemosiderin


Hyaline-walled vessels, amianthoid fibers

SMA+, beta-catenin+, other markers negative


Kaposi sarcoma, intranodal

Children or young adults in lymph node draining skin lesion, or rarely primary generalized lymphadenopathy

Curved fascicles of spindle cells, pleomorphism, and mitoses


Hemorrhage, hyaline globules

HHV8+, CD34+, CD31+, ERG+, SMA−, S100 protein−, CK−


Cellular schwannoma

M > F


Deep soft tissue, retroperitoneum, pelvis, rare in lymph node


Firm mass up to 20 cm diameter


Can recur but does not metastasize

Encapsulated (fragment of capsule often present in core biopsy), subcapsular lymphoid aggregates, sheets of elongated spindle cells with eosinophilic cytoplasm


Clusters of foamy macrophages, lymphocytes

S100 protein+ diffusely, GFAP+, D2-40+, CK+ rarely, EMA+ (subcapsular)


Fibromatosis—desmoid type

Deep soft tissue, limbs, head and neck, body cavities

Parallel-aligned myofibroblasts evenly dispersed in collagen, slitlike and thick-walled vessels, mast cells


No nuclear atypia or necrosis

SMA+, beta-catenin+ in nuclei


CD34−


Low-grade myofibrosarcoma

Head and neck, extremities, retroperitoneum, bone, infiltrative mass, recurs

Cellular fascicles infiltrate muscle


Myofibroblastic morphology, mostly uniform but focal nuclear atypia is diagnostic


Occasional necrosis

SMA+, desmin±, h-caldesmon−, S100 protein−, CD34−


Leiomyosarcoma

Dermis, subcutis, or (mostly) deep soft tissue


Slowly growing


Some related to obvious blood vessel


Recurs

Well-defined fascicles at right angles


Nontapered cells, eosinophilic cytoplasm, nuclear atypia, abnormal mitoses

SMA+, desmin+, h-caldesmon+, CK in some (dot), CD34+ rarely



Pathologic Features

Myofibroma forms a circumscribed nodule up to 5 cm in diameter, and unlike in nodular fasciitis, there can sometimes be central necrosis. Superficial lesions can involve dermis and subcutis (e-Fig. 7.1). Histologically, there is a biphasic pattern with whorled lobules of palely eosinophilic myofibroblastic cells around a central focus of smaller, more darkly staining cells, with ovoid nuclei, scanty cytoplasm, and focal mild pleomorphism, associated with a hemangiopericytomatous pattern (Figs. 7.1 and 7.2, e-Figs. 7.2 to 7.6). Multinucleated cells (e-Figs. 7.5 and 7.6) are occasionally seen and intravascular extension (e-Fig. 7.7) is relatively common. Mitoses can be frequent, and the central necrosis is sometimes extensive, leaving only a thin rim of viable lesional tissue. This can result in hyalinization, calcification, or ossification (e-Fig. 7.8). Some cases show morphologic overlap with myopericytoma.5


Ancillary Investigations

The spindle cells of myofibroma are positive for SMA (e-Fig. 7.9) and negative for desmin, h-caldesmon, CD34, and S100 protein.6 Electron microscopy shows the spindle cells to be myofibroblasts rather than smooth muscle cells, with rough endoplasmic reticulum, stress fibers, and rare fibronexus structures.6,7






FIGURE 7.1 Myofibroma. A zone of closely packed cells merges with paler nodules with peripheral spindle cells. There is a poorly defined hemangiopericytic pattern.







FIGURE 7.2 Myofibroma. Nodules of myofibroblasts with myxoid change and mild inflammation. There is an adjacent more cellular zone with residual vascular pattern.


MYOPERICYTOMA

The concept of hemangiopericytoma as a distinct tumor type has been challenged in recent years, on the basis that a pericytomatous vascular pattern is seen in a wide variety of soft tissue tumor types, and that it is not therefore specific to any cell lineage.8 Many tumors previously termed hemangiopericytoma have been recategorized as solitary fibrous tumor,9 and infantile hemangiopericytoma is now regarded as a variant of myofibroma or, occasionally, myopericytoma. Meanwhile, tumors considered to show true pericytic differentiation have become defined.5,10 The pericyte is a spindle-shaped or rounded cell which surrounds and is closely related to endothelium in capillary blood vessels and can exhibit variable smooth muscle (“myopericytic”10) or glomus-like differentiation. Tumors with pericytic differentiation can therefore resemble leiomyomas, myofibromas, or glomus tumors, often with the addition of a prominent hemangiopericytomatous pattern.5 Since the latter, however, is now regarded as a nonspecific finding unrelated to differentiation, this is presumably adventitious. Myopericytomas can have various combinations of patterns. This has led to division into a number of morphologic subtypes, but these have no prognostic significance.


Clinical Features

Myopericytoma is more common in males, in adult life, and occurs principally in the upper and lower extremities, with occasional cases in the head and neck region and on the trunk. Epstein-Barr virus-associated myofibroma has been described in patients with AIDS.11
Most myopericytomas arise in dermis or subcutis or involve both, with occasional deeper examples. They present as slowly growing single or rarely multiple nodules. The behavior is generally benign, with only an occasional recurrence,12 but rare malignant examples have been described with aggressive behavior.13


Pathologic Features

Myopericytoma is a circumscribed nonencapsulated lesion with variable hemangiopericytomatous vascular pattern, which displays a variety of overlapping cytologic features. In the myofibroma-like variant, the cells are spindle shaped with eosinophilic cytoplasm (Fig. 7.3, e-Figs. 7.10 and 7.11). In the pericytomatous subtype, present is the striking feature of spindle cells with elongated nuclei disposed in concentric layers in the walls of small vessels and spinning off into adjacent tissues, which often contain dilated thin-walled vessels (Figs. 7.4 and 7.5, e-Figs. 7.12 to 7.18). The cells have bland nuclei, indiscernible cell boundaries, and varying amounts of eosinophilic cytoplasm. Other examples display focal or widespread glomus cell differentiation, usually as a single perivascular layer displaying a glomangiomatous pattern (Fig. 7.6, e-Figs. 7.19 and 7.20). They differ from regular glomus tumor in the vascular architecture and usually in having only focal glomus cell differentiation. Enlarged or multinucleated cells can occasionally be seen. Mitoses usually do not exceed 2 per 10 hpf. Rare malignant examples have more mitoses, including atypical forms, nuclear pleomorphism, infiltration, and necrosis.13 Some tumors are predominantly hemangiopericytomatous, and solid,
angiomyoma-like, and hypocellular fibroma-like variants have been defined, but combinations of these patterns can be seen (e-Fig. 7.18).12 The picture can be complicated by the presence of hemorrhage or infarction, hyalinizing fibrosis, edema, or inflammation. Intravascular myopericytoma, arising within a larger vessel, has also been described,14

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Related posts:

  1. Cutaneous Spindle Cell Lesions
  2. Spindle Cell Sarcomas
  3. Soft Tissue Lesions with Clear or Granular Cells
  4. Deep Vascular Lesions

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Jun 18, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Myofibroma, Myopericytic Tumors, Myoepithelioma, and Myofibroblastoma

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