Miscellaneous Tumors of Uncertain Differentiation





Benign tumors


Superficial Angiomyxoma


Definition





  • An uncommon distinct type of myxoma characterized by the presence of thin-walled blood vessels



  • This is likely to represent the same entity as cutaneous myxoma, including the lesions seen in Carney complex



Clinical features


Epidemiology





  • Presents during adulthood and shows slight male predilection



  • Commonly affects the head and neck and trunk areas



Presentation





  • Usually solitary



  • Size: 1 to 5 cm



Prognosis and treatment





  • Benign tumors, but frequently recur locally



  • No reports of metastasis



Pathology


Histology





  • Dermal or subcutaneous lobules of plump, stellate or spindle-shaped, bland-looking cells embedded in basophilic, highly vascular, myxoid matrix



  • Aggregates of inflammatory cells, particularly neutrophils, are commom



  • May contain entrapped epithelial component that resembles keratinous cysts



  • Some consider this equivalent to cutaneous myoma



Immunohistochemistry/special stains





  • Neoplastic cells express vimentin and sometimes CD68, factor XIIIa, and CD34



  • The myxoid stroma can be highlighted with Alcian blue or mucicarmine stains



Main differential diagnoses





  • Aggressive angiomyxoma



  • Angiomyofibroblastoma



  • Low-grade myxofibrosarcoma



  • Nerve sheath myxoma


Fig. 1


Superficial angiomyxoma.

An ill-defined, superficially based, dermal neoplasm composed of lobules of neoplastic cells embedded in a highly vascularized myxoid stroma.



Fig. 2


Superficial angiomyxoma.

Another example with more cellular features.



Fig. 3


Superficial angiomyxoma.

The neoplasm is composed of spindle cells with abundant myxoid stroma.



Fig. 4


Superficial angiomyxoma.

Bland-appearing stellate cells, myxoid stroma, and vascular channels comprise the three elements of this neoplasm.



Fig. 5


Superficial angiomyxoma,

high-power view. Note the lack of atypia and mitoses.




Intramuscular Myxoma


Definition





  • Benign mesenchymal tumor composed of bland, spindle-shaped cells embedded in a characteristically hypovascular myxoid stroma



Clinical features


Epidemiology





  • An exclusively intramuscular neoplasm



  • It usually involves the large skeletal muscles of extremities, particularly the thigh



  • Superficial cases involving head and neck and hypothenar area of the hand are extremely rare



  • Majority of patients are adults



  • Two-thirds of patients are females



  • Rare cases are associated with Mazabraud syndrome (single or multiple intramuscular myxomas and polyostotic fibrous dysplasia)



Presentation





  • Most cases present as slowly growing, painless muscular masses



  • Angiographic studies demonstrate poorly vascularized neoplasms



Prognosis and treatment





  • Surgical excision is virtually always curative



  • Recurrence is unusual even after incomplete resection



  • Cellular variant has a higher tendency for recurrence



Pathology


Histology





  • Classically described as “hypocellular” and “hypovascular” tumor



  • Commonly infiltrates adjacent muscle fibers



  • Abundant myxoid stroma with sparse, capillary-sized blood vessels



  • Uniform, cytologically bland, spindle-shaped cells with eosinophilic cytoplasm



  • A cellular variant has been described



  • Tumors typically lack cytological atypia, mitoses, and necrosis



Immunhistochemistry/special stains





  • Neoplastic cells express vimentin



  • Variable expression with CD34, desmin, and smooth muscle actin



  • S100 protein is not normally expressed



Genetic profile





  • Recurrent point mutations involving the GNAS1 gene are common



Main differential diagnoses





  • Chondrosarcoma



  • Low-grade myxofibrosarcoma



  • Low-grade fibromyxoid sarcoma



  • Myxoid liposarcoma



  • Myxoid neurothekoma


Fig. 1


Intramuscular myxoma.

An intramuscular neoplasm exhibiting abundant myxoid stroma with pseudocystic spaces.



Fig. 2


Intramuscular myxoma.

The classic “hypocellular” and “hypovascular” morphology characteristic of intramuscular myxoma.



Fig. 3


Intramuscular myxoma.

Tumor–muscle interphase showing infiltration of the neoplasm between atrophic skeletal muscle fibers.



Fig. 4


Intramuscular myxoma.

The lesions are usually sparsely cellular.



Fig. 5


Intramuscular myxoma.

Areas of increased cellularity can be encountered, but atypia is not a feature.



Fig. 6


Intramuscular myxoma.

More cellular area composed of spindle cells with prominent eosinophilic cytoplasm.




Juxtaarticular Myxoma


Definition





  • A rare, benign mesenchymal tumor that histologically resembles intramuscular myxoma and usually arises in the vicinity of a joint



Clinical features


Epidemiology





  • Wide age range



  • The majority of affected individuals are males (more than 70%) in their third to fifth decades



  • The most common location is around the knee



  • Mainly involves the periarticular tendons, ligaments, joint capsule, muscles, and the adjacent subcutis



Presentation





  • Most cases present as a mass, sometimes associated with pain



Prognosis and treatment





  • Benign tumors often cured by complete excision



  • Recurrence is common; can be multiple



  • Recurrence usually takes place within 18 months



  • Recurrence commonly involves subcutaneous adipose tissue



Pathology


Histology





  • Histologically virtually identical to intramuscular myxoma



  • Unlike intramuscular myxoma, cystic changes are more common, and rare mitoses as well as atypical reactive cells can be seen



Immunohistochemistry/special stains





  • Alcian blue–positive matrix



  • Neoplastic cells express vimentin



  • Variable expression with CD34, desmin, and smooth muscle actin



  • S100 protein is not normally expressed



Genetic profile





  • Recurrent point mutations involving the GNAS1 gene are not seen



Main differential diagnoses





  • Ganglion cyst



  • Chondrosarcoma



  • Low-grade myxofibrosarcoma



  • Low-grade fibromyxoid sarcoma



  • Myxoid liposarcoma



  • Myxoid neurothekoma


Fig. 1


Juxtaarticular myxoma.

The neoplasm forms lobules involving the articular soft tissue.



Fig. 2


Juxtaarticular myxoma.

The neoplastic lobules are composed of stellate to spindle-shaped cells embedded in a myxoid stroma.



Fig. 3


Juxtaarticular myxoma.

The neoplasm is histologically identical to the cellular variant of intramuscular myxoma.



Fig. 4


Juxtaarticular myxoma.

High-power view of the stellate and spindle-shaped tumor cells.




Ectopic Hamartomatous Thymoma


Definition





  • A rare, suprasternal, heterogeneous tumor composed of an admixture of spindle cells, epithelial cells, and adipose tissue with a presumed branchial origin



  • Despite the name, there is no definite evidence of thymic origin or thymic differentiation



  • The designation branchial anlage mixed tumor has been proposed to describe this entity



Clinical features


Epidemiology





  • Majority of patients are adults



  • Striking male predominance



Presentation





  • Slowly growing, small, lower neck mass



Prognosis and treatment





  • Generally benign lesion



  • Cured by complete resection



  • No reports of metastasis



Pathology


Histology





  • Tumors consist of three haphazardly arranged components: epithelial cell, spindle cell, and adipose tissue



  • Spindle cell component usually predominates



  • The epithelial component consists of either solid or cystic squamous epithelium



  • Glandular structures are less common



  • The spindle cells exhibit bland-looking elongated nuclei



  • Myoid differentiation of spindle cells is sometimes seen



  • Myoepithelial differentiation is uncommon



  • Tumor cells are devoid of pleomorphism



  • Mitoses are usually absent



  • Scattered lymphocytes may be seen



Immunohistochemistry/special stains





  • Both epithelial and spindle cells express cytokeratins, particularly high-molecular-weight forms



  • CD34 is expressed by the spindle cells only



  • Androgen receptor is expressed by the spindle cells



  • Muscle actin and myoglobin can be expressed by spindle cells



  • Desmin and S100 protein are negative



Main differential diagnoses





  • Ectopic cervical thymoma



  • Thymolipoma



  • Teratoma



  • Biphasic synovial sarcoma



  • Malignant peripheral nerve sheath tumor with glandular differentiation



  • Benign mixed tumor/myoepithelioma of soft tissue


Fig. 1


Ectopic hamartomatous thymoma.

This hamartoma is composed of haphazardly arranged epithelial and stromal components. There are true cystic spaces lined by bland-appearing squamous epithelium embedded in a spindle cell stroma. Note the myxoid quality of the stroma and the variably sized blood vessels.



Fig. 2


Ectopic hamartomatous thymoma.

Glandular structures lined by bland-appearing epithelial cells. The stromal cells exhibit prominent myoid differentiation.



Fig. 3


Ectopic hamartomatous thymoma.

Squamous epithelium–lined cystic spaces embedded in an abundant stroma.



Fig. 4


Ectopic hamartomatous thymoma.

A squamous epithelium–lined cyst surrounded by spindle cell stroma. Note the lack of atypia and mitoses.






Intermediate tumors


Hemosiderotic Fibrolipomatous Tumor


Definition





  • Also known as hemosiderotic fibrohistiocytic lipomatous lesion



  • A rare, superficial proliferation composed of spindle cells and adipocytes that almost exclusively involves the ankle



  • An association between myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor reported recently, as both lesions can share an identical translocation at t(1;10)(p22;q24)



Clinical features


Epidemiology





  • Affected individuals are usually adults



  • Predilection for females



Presentation





  • Slowly growing, may be painful



  • Size is variable



  • History of trauma is obtained in up to 70% of cases



Prognosis and treatment





  • Treated by local excision



  • Local recurrence can occur



  • No reports of metastasis



Pathology


Histology





  • Well-circumscribed lobules of mature adipocytes admixed with areas composed of spindle cells



  • The spindle cell areas show striking hemosiderin deposition



  • No or mild atypia



  • No or rare mitoses



  • Sometimes associated with venous stasis and can be histologically virtually identical to early pleomorphic, hyalinizing angiectatic tumor (but is not pathogenically related to this tumor)



  • Hybrid lesions with myxoinflammatory fibroblastic sarcoma can be encountered (the two tumors do appear to be pathogenically related in at least a subset of cases)



Immunohistochemistry/special stains





  • The spindle cells express vimentin, CD34, and calponin



Genetic profile





  • Distinctive translocation t(1;10)(p22;q24) involving the TGFBR3 and MGEA5 genes in the great majority of cases, frequently also associated with amplifications of chromosome 3p11~12, resulting in formation of ring chromosomes (also designated marker chromosomes ) with increased expression of VGLL3 and CHMP2B genes



  • Myxoinflammatory fibroblastic sarcoma can harbor this fusion in a subset of cases



  • TGFBR3-MGEA5 fusions are more commonly encountered in hybrid hemosiderotic fibrolipomatous tumor/myxoinflammatory fibroblastic sarcoma lesions than in classical “pure” myxoinflammatory fibroblastic sarcomas



  • These features suggest a pathogenical relationship between at least a subset of these two tumor types



Main differential diagnoses





  • Spindle cell lipoma



  • Atypical lipomatous tumor


Fig. 1


Hemosiderotic fibrolipomatous tumor.

The lesion is composed of lobules of mature adipose tissue along with fibrous tissue.



Fig. 2


Hemosiderotic fibrolipomatous tumor.

Lobules of mature adipose tissue separated by variably thickened, fibrous septa populated by spindle cells.



Fig. 3


Hemosiderotic fibrolipomatous tumor.

The juxtaposition and intermixing of the lipomatous and spindle cell fibrous components of this lesion are demonstrated here.



Fig. 4


Hemosiderotic fibrolipomatous tumor.

Fibrous area composed of bland-appearing spindle cells that lack atypia and mitosis.



Fig. 5


Hemosiderotic fibrolipomatous tumor.

An inflammatory component is commonly encountered.



Fig. 6


Hemosiderotic fibrolipomatous tumor.

Fibrous area with prominent hemosiderin deposition.



Fig. 7


Hemosiderotic fibrolipomatous tumor.

Mature adipocytes separated by traversing vascularized fibrous component. Scattered inflammatory cells, including mast cells, lymphocytes, and macrophages, are commonly seen.




Deep (Aggressive) Angiomyxoma


Definition





  • A mesenchymal neoplasm composed of stellate or spindle cells that commonly exhibit myoid differentiation embedded in an abundant myxedematous stroma



Clinical features


Epidemiology





  • Affected patients are almost exclusively females 40 to 60 years of age



  • Much less common in women older than 60 years and does not affect children



  • Tumors are usually deeply located in pelvic, perineal, anorectal, or retroperitoneal regions



Presentation





  • Commonly present as asymptomatic, slowly growing mass



  • Patients may present with feeling of pressure, discomfort, or pain



  • Size is variable but often large (>10 cm)



Prognosis and treatment





  • Locally aggressive tumors (intermediate)



  • Recurrence is common, which can be late, but usually not more than once



  • No metastases have been reported



  • Usually managed by surgical excision



  • May respond to hormonal therapy using gonadotropin-releasing hormone agonist



Pathology


Histology





  • Sparsely to moderately cellular neoplasms composed of bland stellate and spindled cells embedded in a loosely collagenized, myxoid matrix with scattered vessels of varied caliber



  • Higher cellularity may be observed at perivascular and peripheral areas



  • Some neoplastic cells show relatively abundant eosinophilic cytoplasm and exhibit fibroblastic and myofibroblastic features and appear to be hormonally influenced



  • Well-developed myoid differentiation best evident around medium-size blood vessels and nerve trunks



  • Mitoses are rare or absent



Immunohistochemistry/special stains





  • Neoplastic cells focally express desmin, smooth muscle actin, muscle specific actin, vimentin, CD34, and estrogen and progesterone receptors



  • S100 protein is negative and Ki-67 index is very low (<1%)



  • The myxoid stroma can often be highlighted with Alcian blue or mucicarmine stains



Main differential diagnoses





  • Superficial angiomyxoma



  • Angiomyofibroblastoma



  • Low-grade myxofibrosarcoma



  • Nerve sheath myxoma


Fig. 1


Deep angiomyxoma.

A moderately to sparsely cellular neoplasm composed of stellate tumor cells embedded in a myxedematous, loosely collagenized stroma.



Fig. 2


Deep angiomyxoma.

A hypocellular area depicting stellate cells embedded in an abundant myxedematous stroma.



Fig. 3


Deep angiomyxoma.

A moderately cellular area showing stellate tumor cells, small-caliber blood vessels, and abundant stroma.



Fig. 4


Deep angiomyxoma.

Variably sized blood vessels can be seen within the neoplasm.



Fig. 5


Deep angiomyxoma.

The neoplastic cells typically lack atypia and mitoses.



Fig. 6


Deep angiomyxoma.

The neoplastic cells express CD34.



Fig. 7


Deep angiomyxoma.

The neoplastic cells commonly exhibit myoid differentiation, demonstrated by the cytoplasmic staining for desmin.




Atypical Fibroxanthoma


Definition





  • Distinctive proliferation confined to the dermis by convention and composed of highly atypical, epithelioid histiocyte–like cells and spindled fibroblast-like cells, in variable proportions, occurring on sun-exposed and sun-damaged skin with invariably benign clinical course



  • Diagnosis is one of exclusion and requires additional immunohistochemistry



  • Mutations in TP53 induced by UVA exposure have been implicated in the pathogenesis



Clinical features


Epidemiology





  • Adult patients, most commonly in the eighth decade of life (mean age 77 years)



  • Male predominance (M:F = 9 : 1)



  • Ultraviolet (UV) irradiation a key factor implicated in pathogenesis



Presentation





  • Sun-exposed and sun-damaged skin



  • Most frequently on the scalp, followed by forehead, ear, nose, and face



  • Rapidly growing polypoid or nodular lesion, frequently ulcerated on the surface



Prognosis and treatment





  • Complete excision usually curative



  • Invariably benign when strict criteria applied



  • Virtually always benign when confined to the dermis



  • Locally aggressive behavior and even metastasis can be seen with significant subcuticular involvement (see Pleomorphic dermal sarcoma later)



Pathology


Histology





  • Admixture of (in variable proportions)




    • Pleomorphic, fibroblast-like spindle cells



    • Histiocyte-like epithelioid cells



    • Multinucleated giant cells




  • Lesional cells growing in sheets and fascicles



  • No connection with the epidermis



  • Numerous mitoses, including atypical ones



  • Tumor necrosis absent



  • Lymphovascular invasion absent



  • Perineural invasion absent



  • Generally well-demarcated proliferation in the dermis



  • Focal, limited extension into superficial subcutis not uncommon and allowed by some authorities




    • Expansile



    • Limited lacelike




  • Surface ulceration in about 50% of cases



  • Epidermal collarette at the periphery of the lesion in 20%, possible extension at variable length along the base of the lesion



  • Solar elastosis, usually marked in the surrounding dermis



  • Diagnosis of exclusion



  • Morphological variants (represent either a focal phenomenon or predominant/exclusive component of the lesion)




    • Spindle cell with more limited pleomorphism




      • Proliferation of monomorphic spindle cells



      • No pleomorphism of conventional atypical fibroxanthoma



      • Fascicular growth of spindle cells with eosinophilic cytoplasm



      • High mitotic activity




    • Pseudoangiomatous or “pigmented” variant with hemosiderin deposition




      • Areas of hemorrhage, usually coupled with hemosiderin deposition



      • Pseudovascular spaces lined by lesional cells (pleomorphic spindle cells, epithelioid cells, multinucleated giant cells)



      • Pleomorphic lesional cells can protrude into the pseudolumina



      • Phagocytosis of hemosiderin and erythrocytes occasionally seen




    • Keloidal




      • Bright eosinophilic, hypocellular/acellular, collagenous, keloidlike areas



      • Usually a focal phenomenon



      • Keloidal areas can be separated from the epidermis by a grenz zone



      • Occasionally in a perivascular distribution




    • Regressing




      • Degree of fibrosis from 10% to 90% of the lesion




        • Thickened collagen bundles with sclerosis (early)



        • Lamellar arrangement of collagen fibers with hyalinization (late)





    • Clear cell change




      • Numerous intracytoplasmic lipid vacuoles in lysosome-rich cells



      • Can also represent a degenerative phenomenon



      • Staining for glycogen uniformly negative




    • Granular cell change




      • Bright eosinophilic granular cytoplasm



      • Likely a degenerative phenomenon related to the accumulation of intracytoplasmic lysosomes




    • Myxoid degeneration




      • Accumulation of hyaluronic acid in the stroma



      • Can be highlighted by periodic acid–Schiff (PAS) or Alcian blue




    • Osteoclast-like giant cells




      • Reactive, osteoclast-like giant cells dispersed among conventional atypical fibroxanthoma



      • True atypical osteoclast-like giant cells also described, likely developing from large, pleomorphic, multinucleated giant cells





Immunohistochemistry/special stains





  • Diagnosis of exclusion: must exclude other mimics by immunohistochemistry



  • By definition, consistently negative for low- and high-molecular-weight cytokeratins, desmin, and S100 protein



  • Reactive S100 protein–positive dendritic cells can on occasion be numerous and should not be mistaken for lesional cells



  • Smooth muscle actin positivity (45%), EMA positivity (24%), usually focal



  • CD99 and CD10 frequently positive, but very nonspecific



  • Cytoplasmic CD31 positivity in about 10%




    • Staining is cytoplasmic and finely granular



    • Not as prominent as in endothelial cells



    • Lesional macrophages can also display cytoplasmic positivity




  • Granular cell variant




    • NKIC3 positive



    • PAS positive after diastase digestion




Main differential diagnoses





  • Squamous cell carcinoma



  • Metaplastic carcinoma



  • Melanoma



  • Angiosarcoma



  • Leiomyosarcoma



  • Undifferentiated (dermal) pleomorphic sarcoma


Fig. 1


Atypical fibroxanthoma.

A polypoid and focally ulcerated, well-demarcated proliferation is seen in the dermis. The tumor always develops in the background of chronic sun-damaged skin.



Fig. 2


Atypical fibroxanthoma.

Limited extension into subcutis can occasionally be present. Extensive infiltration of the subcutis precludes the diagnosis of atypical fibroxanthoma and warrants designation of the tumor as pleomorphic dermal sarcoma.



Fig. 3


Atypical fibroxanthoma.

Solar elastosis is always present in variable degrees in the surrounding dermis. Absence of solar elastosis generally precludes the diagnosis of atypical fibroxanthoma.



Fig. 4


Atypical fibroxanthoma.

The tumor is composed of highly pleomorphic, epithelioid, and spindle cells admixed with multinucleated giant cells.



Fig. 5


Atypical fibroxanthoma.

This example shows predominance of pleomorphic epithelioid cells.



Fig. 6


Atypical fibroxanthoma.

Numerous mitoses are generally seen, including atypical mitoses. By definition, however, areas of necrosis are absent, and there is no perineural or lymphovascular invasion.



Fig. 7


Atypical fibroxanthoma.

This example shows predominance of pleomorphic spindle cells. Note bizarre atypical mitosis.



Fig. 8


Atypical fibroxanthoma.

Pleomorphic tumor cells are frequently seen abutting the epidermis. This should not be misinterpreted as intraepidermal origin of the proliferation.



Fig. 9


Atypical fibroxanthoma.

Another example with admixture of pleomorphic spindled and epithelioid cells. Note extensive ulceration.



Fig. 10


Atypical fibroxanthoma.

Prominent clear cell change is present in this example. The tumor is extensively ulcerated.



Fig. 11


Atypical fibroxanthoma with clear cell change

—higher magnification. Note also pleomorphism and mitotic activity.



Fig. 12


Atypical fibroxanthoma with granular cell change.

Atypical cells are distinguished by granular cytoplasm.



Fig. 13


Atypical fibroxanthoma with keloidal areas.

Classical histological features of atypical fibroxanthoma are present in the upper part of the picture. Extensive keloidal change is seen toward the lower half of the lesion.



Fig. 14


Atypical fibroxanthoma with keloidal areas

—higher magnification. Atypical cells are present in between keloidal collagen.



Fig. 15


Atypical fibroxanthoma

—spindle cell nonpleomorphic variant. This morphological variant is distinguished by proliferation of spindle cells and lack of pronounced cytological pleomorphism. Well-formed collarette can also be appreciated in this example, as well as prominent solar elastosis.



Fig. 16


Atypical fibroxanthoma

—spindle cell nonpleomorphic variant. Note the lack of significant nuclear pleomorphism and the presence of mitotic activity.



Fig. 17


Atypical fibroxanthoma

—pseudoangiomatous variant. Areas of bleeding and pseudovascular spaces lined by the lesional cells displaying striking similarities to angiosarcoma.



Fig. 18


Atypical fibroxanthoma

—pseudoangiomatous variant. Atypical cells displaying mitotic activity appear to be lining the pseudovascular spaces.




Angiomatoid Fibrous Histiocytoma


Definition





  • Uncommon variant of fibrohistiocytic tumor characterized by the presence of cystic hemorrhagic spaces



  • Formerly known as angiomatoid malignant fibrous histiocytoma



Clinical features


Epidemiology





  • Affected patients are children or young adults



  • Tumors are usually located in the subcutaneous tissue of extremities or trunk



  • Deeply situated lesions are less commonly encountered



Presentation





  • Superficial, slow growing



  • Size: few millimeters to 2 cm



  • May be associated with systemic symptoms (fever, anemia, malaise, and weight loss)



Prognosis and treatment





  • Good outcome achieved with simple surgical excision



  • Local recurrence is reported in 10%



  • Deep lesions elicit higher tendency for recurrence



  • Metastasis to local lymph nodes is seen in only 1% of cases



Pathology


Histology





  • Pseudoencapsulated, multicystic, hemorrhagic lesions



  • Neoplastic elements are bland-looking, round or spindle cells admixed with chronic inflammatory cells



  • Inflammatory infiltrates can organize with germinal centers simulating lymph node metastasis



  • Tumor cells may exhibit mild to moderate pleomorphism and occasional mitoses



Immunohistochemistry/special stains





  • Neoplastic cells commonly express CD68, CD99, muscle actin, desmin, EMA, and calponin



  • No reactivity with factor VIII, CD34, CD31, S100 protein, or cytokeratin



Genetic profile





  • t(12;16)(q13;p11) creating ATF1 FUS fusion gene, t(12;22)(q13;q12) creating ATF1 EWSR1 fusion gene, or t(2;22)(q33;q12) creating CREB1 EWSR1 fusion gene—this latter being the most common



Ultrastructure





  • Cells show variable features, including fibroblastic, myofibroblastic, and histiocytic differentiation



Main differential diagnoses





  • Aneurysmal fibrous histiocytoma



  • Angiosarcoma


Fig. 1


Angiomatoid fibrous histiocytoma.

The tumor is surrounded by pseudocapsule and shows cystic hemorrhagic spaces. Lymphocytic aggregates cuffing the lesion are noted here.



Fig. 2


Angiomatoid fibrous histiocytoma.

Prominent lymphocytic infiltrate with occasional germinal center formation mimicking a lymph node with metastatic tumor.



Fig. 3


Angiomatoid fibrous histiocytoma.

The neoplasm is composed of spindle and histiocytoid cells with distinct syncytial growth pattern, along with prominent lymphocytic infiltrate occasionally forming a germinal center.



Fig. 4


Angiomatoid fibrous histiocytoma.

Sheets of spindle cells with pseudoangiectatic, hemorrhagic cystic spaces.



Fig. 5


Angiomatoid fibrous histiocytoma.

Nodular growth of spindle tumor cells along with prominent lymphocytic aggregate.



Fig. 6


Angiomatoid fibrous histiocytoma.

The neoplastic spindle and histiocytoid cells may exhibit mild pleomorphism and occasional mitoses, as depicted in this example.



Fig. 7


Angiomatoid fibrous histiocytoma.

Histiocytoid cellular morphology demonstrating syncytial growth pattern and mild pleomorphism.




Myoepithelioma of Soft Tissue


Definition





  • An uncommon neoplasm with features virtually identical to that of myoepithelial and mixed tumors arising in salivary glands



Clinical features


Epidemiology





  • Tumors can present at any age



  • Generally, uncommon in elderly patients



  • The extremities are most commonly affected



  • The majority of lesions are subcutaneously located



Presentation





  • Wide age range, from toddlers to elderly (median 37 years)



  • Male dominance (M:F about 5:2)



  • Upper extremities, lower extremities, and back most commonly involved



  • Usually less than 3 cm (median 0.8 cm)



Prognosis and treatment





  • Treated with local surgical excision



  • Local recurrence is reported in up to 20% of cases



  • Behavior challenging to predict from histological features



  • Frankly malignant cases are described



Pathology


Histology





  • Tumors show similar morphology to their salivary gland counterparts



  • Fairly circumscribed, focally infiltrative, lobulated architecture



  • Tumors are composed of nests and cords of epithelioid–spindle cells in a variably myxochondroid matrix



  • Ductal formation may be encountered (mixed tumor/chondroid syringoma)



  • Chondroosseous differentiation is occasionally seen



  • Cutaneous syncytial variant




    • Solid or sheetlike growth of uniform ovoid to spindle cells with pale pink cytoplasm and a syncytial appearance



    • Adipocytic metaplasia is common




Immunohistochemistry/special stains





  • The majority of tumors express keratin, calponin, and S100 protein



  • Keratin can be more focal in the syncytial variant or absent altogether



  • EMA, glial fibrillary acid protein, and smooth muscle actin are commonly expressed



  • Loss of INI-1 expression is reported in half of cases



  • Desmin expression is rarely seen



Genetic profile





  • EWSR1 rearranged in 45% of cases with a variety of partners, including




    • EWSR1-POU5F1



    • EWSR1-PBX1



    • EWSR1-KLF17



    • EWSR1-PBX3



    • EWSR1-ATF1



    • Syncytial variant harbors EWSR1 rearrangement likely with alternative partner(s)




  • FUS rearrangements also seen




    • FUS-KLF17



    • FUS-POU5F1




  • PLAG1 gene rearrangement has also been reported (particularly in cases with ductal differentiation)



  • SMARCB1 homozygous deletions in some cases



Main differential diagnoses





  • Extraskeletal myxoid chondrosarcoma



  • Carcinoma



  • Melanoma


Fig. 1


Benign myoepithelioma of soft tissue.

The neoplasm forms a well-circumscribed dermal nodule.



Fig. 2


Benign myoepithelioma of soft tissue.

The overlying epidermis is flattened. There is no involvement of the epidermis by the neoplastic process.



Fig. 3


Benign myoepithelioma of soft tissue.

Base of tumor shows well-demarcated tumor border. The presence of an infiltrative border should raise the suspicion of malignancy.



Fig. 4


Benign myoepithelioma of soft tissue.

The myoepithelioma neoplastic cells exhibit a wide spectrum of cytological morphology. In this example, the neoplastic cells are spindle shaped. Mitoses or atypias are not typically seen in benign myoepithelioma.



Fig. 5


Malignant myoepithelioma of soft tissue.

The neoplasm is infiltrating the subcutaneous adipose tissue. A myxoid stroma is noted in this example.



Fig. 6


Malignant myoepithelioma of soft tissue.

Admixture of round, small cells with scanty cytoplasm and larger cells with more abundant, occasionally vacuolated cytoplasm. The wide range of morphological spectrum is characteristic of myoepithelial neoplasms.



Fig. 7


Malignant myoepithelioma of soft tissue.

Neoplastic cells exhibiting clear cell morphology. The cells have centrally located, mildly atypical nuclei surrounded by clear cytoplasm.



Fig. 8


Malignant myoepithelioma of soft tissue.

These neoplastic cells exhibit a plasmacytoid morphology. The cells have eccentrically located, hyperchromatic nuclei and abundant eosinophilic cytoplasm.



Fig. 9


Malignant myoepithelioma of soft tissue.

The majority of myoepithelial tumors show strong keratin expression by the tumor cells.



Fig. 10


Malignant myoepithelioma of soft tissue.

The myoepithelial cells express nuclear and cytoplasmic S100 protein.



Fig. 11


Malignant myoepithelioma of soft tissue.

A subset of myoepithelial tumors shows smooth muscle actin expression. This example shows focal expression of smooth muscle actin by the tumor cells.




Ossifying Fibromyxoid Tumor


Definition





  • A rare subcutaneous tumor of uncertain line of differentiation characterized by a peripheral shell of woven bone and a lobular proliferation of bland, round cells embedded in a fibromyxoid matrix



  • An incomplete Schwannian and/or chondroid line of differentiation has been suggested



  • A rare malignant counterpart has been described



Clinical features


Epidemiology





  • Trunk and proximal extremities are commonly affected



  • Patients present in their middle age



  • Male predilection is noted



Presentation





  • Painless, small lesions



  • Size: few millimeters to 3 cm



Prognosis and treatment





  • Most cases show benign clinical behavior



  • Atypical and frankly malignant tumors tend to recur and metastasize to lungs



Pathology


Histology





  • Well-circumscribed lobules composed of small, round to polygonal cells embedded in a richly vascularized fibromyxoid matrix



  • A shell of metaplastic bone is seen in two-thirds of cases



  • Mitoses are fewer than 2 per 50 high-power fields



  • Chondroid differentiation is a rare phenomenon



  • Malignant cases exhibit increased cellularity, atypia, mitoses, necrosis, and invasion of vascular spaces



Immunohistochemistry/special stains





  • Neoplastic cells express S100 protein and desmin



Genetic profile





  • Variety of fusion transcripts reported




    • EP400 PHF1 (≈40 %)



    • Less common




      • ZC3H7B-BCOR



      • MEAF6-PHF1



      • EPC1-PHF1



      • CREBBP-BCORL1



      • KDM2A-WWTR1





Main differential diagnoses





  • Extraskeletal myxoid chondrosarcoma



  • Chondroid syringoma



  • Melanocytic neoplasia


Fig. 1


Benign ossifying fibromyxoid tumor.

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Oct 29, 2019 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Miscellaneous Tumors of Uncertain Differentiation
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