Leiomyoma

Clinical Features

Cutaneous leiomyomas may be sporadic or hereditary and typically arise in young to middle-aged adults. Sporadic leiomyomas may be solitary or multiple and usually present as painful papules or nodules on the extensor surface, head and neck, or trunk. A second subset of leiomyomas arises in the genital skin or the nipple. In contrast to leiomyomas arising at most cutaneous sites, tumors in these locations tend to be painless. Genital tumors are discussed in more detail in Chap. 11. Heritable forms present as multiple lesions and are associated with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome , also known as multiple cutaneous and uterine leiomyomatosis syndrome (Reed syndrome ), which is an autosomal dominant disorder related to mutations of the fumarate hydratase gene. Almost all affected women with this disorder have uterine leiomyomas, and close to 80% of patients have cutaneous manifestations. Between 10% and 34% of patients have renal cell carcinoma, typically papillary type 2 renal cell carcinoma. The renal tumors usually present in middle age and have a 70% mortality rate. Other tumors associated with the syndrome include urothelial carcinoma, prostate carcinoma, gastrointestinal stromal tumor, pheochromocytoma, testicular Leydig cell tumor, adrenal adenoma, ovarian cystadenoma, and benign renal cysts. Cutaneous leiomyomas are frequently the presenting sign of the syndrome. The presence of cutaneous leiomyomas should prompt investigation of the patient’s clinical history to determine if additional testing to rule out HLRCC syndrome is warranted. Cutaneous leiomyomas are benign and may be cured by simple excision if it is clinically practical to excise in the case of multiple lesions.

Pathologic Features

Cutaneous leiomyomas may be comprised of pilar or genital/nipple smooth muscle. The pilar leiomyomas are composed of a poorly circumscribed proliferation of haphazard intersecting fascicles of histologically bland smooth muscle tissue in the reticular dermis (Fig. 13.1a). The tumor cells are spindle shaped and have elongated blunt-ended (cigar-shaped) nuclei with abundant eosinophilic cytoplasm (Fig. 13.1b). Occasional tumor cells may show perinuclear cytoplasmic vacuoles. Genital and nipple leiomyomas are similar in appearance. Genital tumors are discussed in more detail in Chap. 11.

Fig. 13.1
figure 1

Leiomyoma. (a) Poorly circumscribed proliferation of smooth muscle bundles in the dermis. (b) Higher-power image demonstrating intersecting fascicles and bland nuclear features

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There is no reliable way to morphologically distinguish sporadic leiomyomas from those associated with HLRCC syndrome . However, the latter tend to have slightly increased nuclear atypia (Fig. 13.2a), but this is not a reliable discriminator. The uterine leiomyomas associated with HLRCC often have prominent nucleoli, unlike non-HLRCC-associated uterine leiomyomas. While genetic testing is the gold standard, immunostains for fumarate hydratase may be utilized, with HLRCC-associated tumors lacking expression in comparison to sporadic tumors (Fig. 13.2b). The sensitivity and specificity of immunohistochemical stains for fumarate hydratase are approximately 83% and 75%, respectively. Both sporadic leiomyomas and HLRCC-associated leiomyomas are positive for SMA, desmin, and h-caldesmon. Rare cases may be positive for cytokeratin, but these lesions are consistently negative for S100 protein, SOX10, and CD34 (Table 13.1).

Fig. 13.2
figure 2

Leiomyoma associated with HLRCC syndrome . (a) Leiomyomas with this syndrome tend to have increased nuclear atypia compared with sporadic leiomyomas. (b) Immunostains for fumarate hydratase are typically negative in the neoplastic cells

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Table 13.1 Key pathologic features : leiomyoma
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Differential Diagnosis

The primary differential diagnosis is with cutaneous leiomyosarcoma (see below). Leiomyosarcomas have more atypia and mitotic activity than leiomyomas. It should be stated that rare (≤1 per 10 HPF) mitotic figures may be seen in cutaneous leiomyomas. Leiomyomas may have degenerative atypia, leading to designation as so-called symplastic leiomyomas . Diagnostic criteria for cutaneous symplastic leiomyomas are not well established. It is our recommendation that this diagnosis be approached with caution. Any significant atypia should warrant conservative but complete excision.

Dermatomyofibroma (see Chap. 4) has horizontally oriented fascicles of myofibroblasts rather than an intersecting growth pattern. The tumor cells of dermatomyofibroma are usually desmin negative.

Congenital Smooth Muscle Hamartoma

Clinical Features

Congenital smooth muscle hamartoma most commonly presents in the lumbosacral region or proximal extremities of infants, as an indurated plaque with perifollicular papules. Coarse hairs may be present.

Pathologic Features

Microscopically, these lesions resemble pilar leiomyomas , being composed of poorly circumscribed, haphazardly arranged fascicles of bland smooth muscle cells (Fig. 13.3a, b). There is sometimes overlying epidermal change consisting of hyperkeratosis, acanthosis, and hyperpigmentation (Table 13.2).

Fig. 13.3
figure 3

Smooth muscle hamartoma . (a, b) Composed of smooth muscle bundles haphazardly arranged in the dermis

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Table 13.2 Key pathologic features : congenital smooth muscle hamartoma
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Differential Diagnosis

Clinical presentation in infancy readily allows distinction from pilar leiomyoma. Congenital smooth muscle hamartoma also shares features with Becker nevus, but this entity also presents later in life and has more prominent epidermal change.

Epstein-Barr Virus-Associated Smooth Muscle Tumors

Clinical Features

Epstein-Barr virus (EBV)-associated smooth muscle tumors occur in the setting of immunosuppression, usually in the setting of AIDS and organ transplantation. Typically, they are deep soft tissue tumors, but rare presentation in the skin can occur. HIV-infected children may be particularly at risk. These lesions were formerly divided into benign and malignant tumors based on morphologic features, such as mitotic activity. It is now recognized that they are clinically indolent, provided that the underlying immunosuppression can be adequately addressed. There are rare reports of metastasis in the setting of HIV infection, but it is likely that these so-called metastatic lesions reflect multiple infectious events analogous to Kaposi sarcoma.

Pathologic Features

Histopathologically, Epstein-Barr virus (EBV)-associated smooth muscle tumors most commonly resemble angioleiomyoma (Fig. 13.4), but they may also resemble leiomyoma or leiomyosarcoma. Intratumoral lymphocytes are sometimes present. By immunohistochemistry, they are positive for smooth muscle markers. EBV RNA in situ hybridization (EBER-CISH) can be utilized to confirm the diagnosis (Table 13.3).

Fig. 13.4
figure 4

EBV-associated smooth muscle tumor resembling angioleiomyoma . Note the intratumoral lymphocytes. (Courtesy of Dr. Wayne Grayson, Ampath National Laboratories, Johannesburg, South Africa)

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Table 13.3 Key pathologic features : EBV-associated smooth muscle tumors
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Differential Diagnosis

The differential diagnosis depends on the predominant histologic features but generally includes angioleiomyoma, leiomyoma, and leiomyosarcoma. Knowledge of the clinical setting of immunosuppression should prompt consideration of EBER-CISH as a confirmatory test. The other entities in the differential diagnosis are not EBER-positive.

Leiomyosarcoma

Clinical Features

Superficial leiomyosarcomas are separated into those arising in the dermis and those arising in the subcutis. Those arising in the dermis are also called cutaneous leiomyosarcoma . These tumors usually arise in young adults in the extremities. They may be painful like pilar leiomyomas. The tumors arising in the subcutis present in older patients as subcutaneous masses, again most often involving the extremities. Metastatic leiomyosarcoma from deep soft tissue or uterine primary tumors has also been described.

The behavior of these lesions differs markedly depending on the anatomic location. Cutaneous leiomyosarcomas confined to the dermis have a risk of local recurrence, but essentially no risk of metastasis. For this reason some authors have proposed classifying them as “pleomorphic dermal smooth muscle tumors.” However, there are rare reports of cutaneous leiomyosarcomas that have metastasized, typically those that show infiltration into the subcutis. We therefore prefer nomenclature that retains the term leiomyosarcoma. When reporting such cases, we comment on the low risk of aggressive behavior and recommend conservative but complete excision with clinical follow-up.

Leiomyosarcomas arising in the subcutis , however, behave in a distinctly different fashion. They arise from vascular smooth muscle and often demonstrate aggressive behavior with a mortality rate up to 50%.

Pathologic Features

The pathologic features depend on where the tumor arises. Cutaneous leiomyosarcomas somewhat resemble pilar leiomyomas . They are poorly circumscribed and usually composed of intersecting fascicles of tapered spindled cells with eosinophilic cytoplasm. They have increased nuclear atypia and mitotic activity, but necrosis and marked atypia are uncommon (Fig. 13.5). Tumors arising in the subcutis are variably infiltrative, and origin from a vessel wall is evident in some cases (Fig. 13.6). They often, though not invariably, have more pleomorphism and mitotic activity than their dermal counterparts. Rare cases have an epithelioid morphology (Table 13.4).

Fig. 13.5
figure 5

Cutaneous leiomyosarcoma . (a) Intersecting fascicles of atypical smooth muscle with enlarged hyperchromatic nuclei. (b) Mitotic figures are typically conspicuous

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Fig. 13.6
figure 6

Leiomyosarcoma arising within a vessel in subcutaneous tissue

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Table 13.4 Key pathologic features : leiomyosarcoma
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Metastatic leiomyosarcoma may involve the dermis or subcutis. Dermal metastases tend to be more circumscribed and have more pleomorphism than primary cutaneous leiomyosarcomas (Fig. 13.7).

Fig. 13.7
figure 7

Metastatic leiomyosarcoma . Metastatic tumors often show more atypia and are more circumscribed compared with primary cutaneous leiomyosarcomas

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Differential Diagnosis

Cutaneous leiomyomas with focal atypia need to be distinguished from cutaneous leiomyosarcoma. The latter has more diffuse atypia and greater mitotic activity. Atypical fibroxanthomas have a more random storiform to fascicular growth pattern rather than intersecting fascicles and a different clinical presentation. It should be noted that atypical fibroxanthoma is commonly positive for SMA, typically in a myofibroblastic “tram-track” pattern, but usually negative, or only focally positive, for desmin. Similarly, spindle cell squamous cell carcinomas may express SMA in this pattern but are typically desmin negative. Also, spindle cell squamous cell carcinomas do not have the intersecting fascicular pattern typical of cutaneous leiomyosarcoma . It should be pointed out that rare cases of leiomyosarcoma can be focally keratin positive. Spindle cell melanomas are positive for S100 protein and SOX10. The tumor cells of cellular fibrous histiocytoma are less eosinophilic and negative for desmin. Peripheral collagen trapping, seen in cellular fibrous histiocytoma, is not seen in cutaneous leiomyosarcoma.

Subcutaneous leiomyosarcomas should be differentiated from undifferentiated pleomorphic sarcoma, soft tissue leiomyoma, and nodular fasciitis. Undifferentiated pleomorphic sarcoma usually has more diffuse pleomorphism and lacks an intersecting fascicular growth pattern. In certain cases immunostains may be required. Immunoreactivity for both SMA and desmin helps identify leiomyosarcoma. Soft tissue leiomyomas are quite rare. Any atypia and mitotic activity in a deep soft tissue smooth muscle tumor suggests the possibility of leiomyosarcoma, with perhaps pediatric tumors being the lone exception. Deep soft tissue leiomyomas may have rare mitotic figures. Nodular fasciitis sometimes is confused with leiomyosarcoma due to increased mitotic activity and immunoreactivity for SMA (usually in a myofibroblastic tram-track pattern). Nodular fasciitis has a loose storiform growth pattern with hemorrhage, myxoid stroma, and cystic breakdown, features not typical of leiomyosarcoma. The tumor cells of nodular fasciitis have more delicate, amphophilic cytoplasm and do not have nuclear atypia.

Rhabdomyoma

Clinical Features

Most rhabdomyomas present in deep soft tissue or the heart. The extra-cardiac cases are subdivided into adult and fetal types. Both types usually involve the head and neck and are more common in males. In the adult type , the tumors most commonly involve the salivary glands and oral cavity. The fetal type tends to present around the ear or orbit. These are benign tumors cured by simple excision.

Pathologic Features

The adult type is composed of large, polygonal cells with small nuclei and abundant eosinophilic cytoplasm with evident cross striations (Fig. 13.8). The fetal type is composed of variable amounts of immature round to spindled rhabdomyoblasts set in a myxoid stroma (Fig. 13.9a, b). They are immunoreactive for desmin, myoglobin, and muscle-specific actin. They may also be focally positive for SMA and S100 protein (Table 13.5).

Fig. 13.8
figure 8

Adult rhabdomyoma characterized by large, polygonal cells with abundant eosinophilic cytoplasm

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Fig. 13.9
figure 9

Fetal rhabdomyoma . (a) Fetal rhabdomyoma predominantly composed of primitive, round rhabdomyoblasts. (b) Example of fetal rhabdomyoma composed predominantly of spindled rhabdomyoblasts

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Table 13.5 Rhabdomyoma : key pathologic features
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Differential Diagnosis

Adult rhabdomyoma could potentially be confused with granular cell tumor. The granular nature of the cytoplasm of the latter and immunoreactivity for SOX10 easily allow distinction. Pleomorphic rhabdomyosarcoma has more nuclear atypia and mitotic activity. The lack of nuclear pleomorphism and mitotic activity also distinguishes fetal-type rhabdomyoma from embryonal rhabdomyosarcoma .

Rhabdomyomatous Mesenchymal Hamartoma

Clinical Features

This is a rare congenital lesion that presents on the head and neck in neonates and infants as a polyp resembling an acrochordon. Most present on the central face, but rare lesions involving the digits, vagina, and sternoclavicular area have been reported.

Pathologic Features

The tumor is composed of mature skeletal muscle with variable admixed adipose and fibrous tissue in the reticular dermis (Fig. 13.10) (Table 13.6).

Fig. 13.10
figure 10

Rhabdomyomatous mesenchymal hamartoma composed of elongated mature skeletal muscle fibers in the reticular dermis. (Courtesy of Dr. Cheryl Coffin, Vanderbilt University)

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Table 13.6 Key pathologic features : rhabdomyomatous mesenchymal hamartoma
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Differential Diagnosis

Rhabdomyomas may be considered in the differential diagnosis , as these tumors also most commonly present in the head and neck. However, they tend to be more deeply situated and do not present as cutaneous polypoid lesions. Adult-type rhabdomyomas have more polygonal cells, and fetal-type rhabdomyomas have immature spindled rhabdomyoblasts rather than the mature skeletal muscle of rhabdomyomatous mesenchymal hamartoma.

Cutaneous Rhabdomyosarcoma

Clinical Features

Primary cutaneous rhabdomyosarcoma is rare, and it is critical to exclude a metastasis before establishing this diagnosis. Like its deep soft tissue counterpart, there is a bimodal age distribution, with young patients and the elderly mainly being affected. Embryonal and alveolar rhabdomyosarcomas affect infants to teenaged children. Cutaneous embryonal rhabdomyosarcomas most commonly involve the head and neck, whereas the alveolar subtype usually arises in the extremities. Both subtypes may present in other cutaneous locations as well. In adults, the most common subtype reported is pleomorphic rhabdomyosarcoma , which often involves the head and neck and extremities. Only rare cases of cutaneous epithelioid rhabdomyosarcoma have been described. In our experience, they are more common in the head and neck. With the exception of the botryoid forms of embryonal rhabdomyosarcoma , the clinical presentation is not distinctive, with most lesions presenting as a cutaneous nodule or mass. While it is difficult to compare behavior of cutaneous rhabdomyosarcoma with deep soft tissue rhabdomyosarcoma due to their rarity, they appear to behave aggressively, with metastasis and/or significant mortality reported for all subtypes.

Pathologic Features

The histologic features are dependent on the subtype. Embryonal rhabdomyosarcoma is composed of uniform round to spindled cells with scant cytoplasm with alternating cellular and myxoid zones (Fig. 13.11a, b). Rhabdomyoblasts characterized by polygonal or spindled tumor cells with abundant eosinophilic cytoplasm may be present or entirely absent. Alveolar rhabdomyosarcoma is typically composed of aggregates of tumor cells separated by fibrous septa (Fig. 13.12). At the periphery of the aggregates, the tumor cells adhere to the surrounding stroma but are dyshesive centrally, resulting in the characteristic alveolar pattern. In some cases this pattern is absent or only focally present. The individual tumor cells have round to oval nuclei, which are somewhat larger and more atypical than the nuclei seen in embryonal rhabdomyosarcoma . Multinucleated tumor cells are also common and are a helpful diagnostic feature when present. Rhabdomyoblasts may be seen but are absent in the majority of cases. Pleomorphic rhabdomyosarcoma is composed of sheets of pleomorphic cells with abundant eosinophilic cytoplasm (pleomorphic rhabdomyoblasts) (Fig. 13.13). Epithelioid rhabdomyosarcoma is characterized by a sheetlike growth pattern of uniform but atypical epithelioid tumor cells with vesicular nuclei, prominent nucleoli, and relatively abundant amphophilic to eosinophilic cytoplasm (Fig. 13.14) (Table 13.7).

Fig. 13.11
figure 11

Embryonal rhabdomyosarcoma (a) Low-power image demonstrating tumor cells in myxoid stroma involving the dermis. (b) High-power image demonstrating small relatively uniform round rhabdomyoblasts in myxoid stroma

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Fig. 13.12
figure 12

Alveolar rhabdomyosarcoma characterized by dyshesive nests of tumor cells in an alveolar pattern

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Fig. 13.13
figure 13

Pleomorphic rhabdomyosarcoma . (a) Sheetlike growth pattern of tumor cells in the dermis. (b) High-power image demonstrating pleomorphic rhabdomyoblasts with abundant eosinophilic cytoplasm

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Fig. 13.14
figure 14

Epithelioid rhabdomyosarcoma . (a) Low-power image demonstrating sheetlike proliferation of epithelioid tumor cells in the dermis. (b) High-power image demonstrating epithelioid to spindled tumor cells with uniform nuclei that have prominent nucleoli

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Table 13.7 Key pathologic features : cutaneous rhabdomyosarcoma
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By immunohistochemistry , all forms of rhabdomyosarcoma are positive for desmin and at least one specific skeletal muscle marker, myogenin and/or MYOD1. It should be noted that immunoreactivity for myogenin and MYOD1 is often patchy. Rhabdomyosarcomas are frequently positive for muscle-specific actin and variably positive for myoglobin as well. As a caveat, immunoreactivity for SMA, cytokeratin, neuroendocrine markers, CD99, and S100 protein may also be seen. When present, immunoreactivity for S100 protein and cytokeratin tends to be focal.

Most alveolar rhabdomyosarcomas have a recurrent t(2;13)(q35;q14) translocation resulting in a PAX3-FOXO1 fusion. A variant t(1;13)(p36;q14) with a PAX7-FOXO1 fusion is seen in a subset. Using break-apart FISH probes to detect the translocation can help confirm the diagnosis of alveolar rhabdomyosarcoma. However, cases morphologically consistent with the alveolar subtype may lack the translocation. In this setting the diagnosis should be based on the morphologic and immunohistochemical features. The other rhabdomyosarcoma subtypes lack recurring translocations.

Differential Diagnosis

The differential diagnosis is dependent on the subtype. Embryonal and alveolar rhabdomyosarcoma needs to be distinguished from other small round blue cell tumors, especially Ewing sarcoma. Ewing sarcoma is diffusely positive for CD99 in a membranous pattern and typically negative for desmin. While desmin immunoreactivity has been reported in Ewing sarcoma, it is uncommon and, when present, usually only focal. Ewing sarcoma is negative for skeletal muscle-specific markers and also has rearrangement of EWSR1, which can be detected by FISH or RT-PCR.

Pleomorphic and epithelioid rhabdomyosarcomas primarily need to be distinguished from sarcomatoid carcinoma and melanoma. This can be complicated by focal cytokeratin immunoreactivity seen in rhabdomyosarcoma. It is important to always consider the possibility of pleomorphic rhabdomyosarcoma if pleomorphic tumor cells with abundant eosinophilic cytoplasm are present. In that situation, we recommend adding a desmin stain to screen for the possibility of rhabdomyosarcoma, followed by stains for myogenin and/or MYOD1 if there is strong desmin positivity.

The differential diagnosis of epithelioid rhabdomyosarcoma is more difficult. Carcinomas or melanomas with morphology resembling epithelioid rhabdomyosarcoma would be expected to have more diffuse immunoreactivity for cytokeratins and expression of melanocyte-specific markers, respectively. In the absence of expected results of immunohistochemical stains in an epithelioid malignancy, addition of a desmin stain may prove useful. Rare cases of true rhabdomyosarcomatous /rhabdomyoblastic differentiation have been reported in melanocytic nevi, Merkel cell carcinoma, and other cutaneous carcinomas. It is therefore imperative to identify the precursor lesion for accurate diagnosis.

Soft Tissue Chondroma

Clinical Features

Soft tissue chondromas usually occur in the hands and feet of middle-aged adults. They are benign lesions, but local recurrence has been reported.

Pathologic Features

Soft tissue chondromas are well-circumscribed tumors arising in the dermis or subcutis. They are composed of mature hyaline cartilage, but hypercellularity and focal nuclear atypia, including binucleated chondrocytes, are commonly present (Fig. 13.15a, b). These features are not indicative of malignancy in this clinical setting. Calcification and ossification are also commonly seen. By immunohistochemistry, they are positive for S100 protein and ERG. They are negative for cytokeratins, desmin, and SMA (Table 13.8).

Fig. 13.15
figure 15

Chondroma . (a) Chondromas are characterized by a lobular proliferation of chondrocytes. (b) Some atypia is a common finding in chondromas and is not indicative of malignancy

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Table 13.8 Key pathologic features : soft tissue chondroma
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Differential Diagnosis

Diagnosis of soft tissue chondroma is typically straightforward. Knowledge that atypia and hypercellularity may be seen helps avoid the erroneous diagnosis of chondrosarcoma. Chondrosarcomas do not present as small nodules in the hands and feet. Myoepitheliomas and cutaneous mixed tumors may have a chondroid matrix, but generally have evidence of epithelial differentiation either by morphology or immunohistochemistry.

Extraskeletal Myxoid Chondrosarcoma

Clinical Features

Extraskeletal myxoid chondrosarcoma usually arises in the deep soft tissue of the proximal extremities/limb girdles in adults, but occasional cases may arise in the subcutis. The M:F ratio is 2:1. Local recurrence is common, as is late (>5 years post-diagnosis) metastasis. For this reason, patients need lifelong follow-up.

Pathologic Features

The tumor has a lobular growth pattern and is composed of cords and nests of uniform epithelioid cells arranged in an abundant myxoid stroma (Fig. 13.16a, b). The tumor cells have uniform round to slightly spindled nuclei and eosinophilic cytoplasm. Intratumoral hemorrhage is commonly present (Fig. 13.16c). The mitotic rate is typically low.

Fig. 13.16
figure 16

Extraskeletal myxoid chondrosarcoma (a) The tumor cells are typically arranged in cords and nests in a myxoid stroma. (b) The tumor is composed of uniform round to oval tumor cells with eosinophilic cytoplasm. (c) Intratumoral hemorrhage is a common finding

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Immunohistochemistry plays little to no role in the diagnosis. Less than 20% of cases show focal immunoreactivity for S100 protein or EMA. Occasional cases may show immunoreactivity for neuroendocrine markers. The only consistently positive marker is vimentin, which is entirely nonspecific and generally of no diagnostic utility.

About 70% of extraskeletal myxoid chondrosarcomas have a recurring t(9;22)(q22;q12) most commonly resulting in a NR4A3-EWSR1 fusion . A minority of cases have a t(9;17)(q22;q11) with a NR4A3-TAF2N fusion . Molecular studies to detect rearrangement of NR4A3 are useful in confirming the diagnosis (Table 13.9).

Table 13.9 Key pathologic features : extraskeletal myxoid chondrosarcoma
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Differential Diagnosis

The primary differential diagnosis is soft tissue myoepithelioma and myxoid liposarcoma . Myoepitheliomas are typically positive for S100 protein and cytokeratin or EMA and are variably positive for SMA and p63. Most extraskeletal myxoid chondrosarcomas are negative for these markers. Myoepitheliomas do not have rearrangement of NR4A3, but it should be remembered that they may have rearrangement of EWSR1. Myxoid liposarcoma only exceptionally presents as a superficial mass and typically has a uniform plexiform vasculature and lipoblasts, which are not seen in extraskeletal myxoid chondrosarcoma. Myxoid liposarcoma also demonstrates rearrangement of DDIT3, which is not found in extraskeletal myxoid chondrosarcoma.

Osteoma Cutis

Clinical Features

Osteoma cutis is not strictly a neoplasm but a reactive process. It can be seen in a variety of settings. It is a frequent finding in facial skin in patients with a history of acne. If multiple lesions are encountered in young children, the possibility of underlying Albright hereditary osteodystrophy should be considered.

Pathologic Features

Osteoma cutis consists of nodules of mature lamellar bone. Some may contain marrow spaces (Fig. 13.17) (Table 13.10).

Fig. 13.17
figure 17

Osteoma cutis composed of fragments of mature bone that sometimes has marrow elements, as in this case

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Table 13.10 Key pathologic features : osteoma cutis
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Differential Diagnosis

Osteoma cutis can be mistaken for dystrophic calcification if the presence of bone is not recognized.

Extraskeletal Osteosarcoma

Clinical Features

Although usually a deep soft tissue tumor, cutaneous extraskeletal osteosarcoma has been reported. It usually occurs in older adults; presentation in younger patients should prompt consideration of metastasis from an underlying bone tumor. Some cutaneous tumors represent metastasis from deep soft tissue or bone primaries. Roughly 10% of cases arise in the setting of prior radiotherapy, and cases associated with scars have been described. This is a potentially aggressive tumor. Although data are lacking regarding behavior of cutaneous examples, extraskeletal osteosarcoma has an overall mortality rate of approximately 75%.

Pathologic Features

Extraskeletal osteosarcoma is composed of atypical spindled to ovoid pleomorphic cells and is associated with malignant osteoid formation (Fig. 13.18a, b). Occasional cases may also show chondroid matrix production (chondroblastic osteosarcoma). Osteoclasts may be present in variable numbers and numerous in rare cases. The tumor cells are positive for SATB2 (Table 13.11).

Fig. 13.18
figure 18

Extraskeletal osteosarcoma (a) Hyperchromatic spindled cells admixed with malignant osteoid. (b) High-power image of a different case with hyperchromatic to spindled cells with lacelike osteoid

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Table 13.11 Key pathologic features : extraskeletal osteosarcoma
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Differential Diagnosis

The primary differential diagnosis is undifferentiated pleomorphic sarcoma. Recognition of malignant osteoid excludes this diagnosis. Cutaneous carcinosarcoma , defined as a distinctly biphasic tumor composed of carcinoma (especially basal cell carcinoma) and sarcoma components, may show osteosarcomatous differentiation. Recognition of the carcinoma component is the key to the correct diagnosis. Distinction is not trivial as carcinosarcoma is less aggressive than extraskeletal osteosarcoma. Other bone-forming tumors can also be considered in the differential diagnosis. Ossifying fibromyxoid tumor, including malignant variants, usually does not display the degree of cytologic atypia seen in extraskeletal osteosarcoma. Also, the bone formation tends to be at the periphery of the lesion. Similarly, giant cell tumor of soft tissue has less atypia with peripheral bone rather than malignant osteoid. Fibro-osseous pseudotumor presents on the digits and lacks the atypia and pleomorphism of extraskeletal osteosarcoma.