Solitary fibrous tumor (SFT) is a fibroblastic neoplasm initially described in pleura, and may occur in almost any site of the body besides the pleura. SFT occurs usually in adults and is less common in children and adolescents. The common sites include subcutaneous tissue (40% of cases) and deep soft tissue of the lower extremities, head and neck region, mediastinum, and retroperitoneum. Tumors previously designated haemangiopericytoma, and the less common lipomatous haemangiopericytoma, are now classified as SFT and lipomatous “fat forming” SFT. The majority of SFT are benign, but approximately 5–10% behave in a malignant fashion, and both malignant and dedifferentiated forms have been reported [12–15].

The aspirate yields variably cellular smears containing bland “fibroblast-like” spindle cells, either dispersed and in loosely cohesive or tight clusters and fascicles (Figs. 5.10, 5.11, and 5.12). The majority of cells display spindle-cell morphology, but a minor component of polygonal cells is a common finding in smears (Fig. 5.13). The tumor cells contain spindle or ovoid nuclei, scanty-to-moderate cytoplasm, and bland nuclei with finely dispersed chromatin and absent or indistinct nucleoli. Naked nuclei, ropy collagen fibers, and mast cells are common. Mild-to-moderate variability in nuclear size and shape may occur, but significant nuclear pleomorphism, necrosis, or mitoses are absent (Table 5.2).

The cells are fibroblast-like, almost always positive for CD34 and STAT6 (nuclear positivity), and a considerable number of cases are positive for CD99 and bcl-2. Tumor cells occasionally display focal positivity for SMA and EMA. Positivity for CD34 may be decreased or lost in malignant variant. SFT are negative for CD117, DOG1, S100, desmin, and keratins [16]. Majority SFTs display an inversion at the 12q13 which results in a fusion gene NAB2-STAT6 [17].

The main differential diagnoses include monophasic fibrous synovial sarcoma, low-grade malignant peripheral nerve sheath tumor (MPNST), and desmoid-fibromatosis. The cellular and nuclear atypia is usually less marked in smears of monophasic synovial sarcoma displaying usually striking uniformity of the tumor cells, while MPNST displays more atypia and nuclear pleomorphism than in SFT. Desmoid-fibromatosis yields fewer cellular smears, often containing more abundant collagenous stroma.

The cytomorphology of SFT as reported is predominantly based on few small series and some case reports [5–8]. The cytological examination of SFT, which often share clinical and microscopic characteristics with other spindle cell neoplasm in soft tissue, is a challenge [17–20]. A correct diagnosis of SFT is difficult to render from routinely stained FNA smears and cell block preparation is helpful to capture the characteristic architectural pattern of SFT of cellular areas of bland spindle cells alternating with fibrotic areas and blood vessels. In addition, strong and diffuse immunoreactivity of tumor cells for CD34 in cell block sections confirms cytological diagnosis [19] (Figs. 5.14 and 5.15).

Smears from a fat forming variant of SFT, formerly named lipomatous haemangiopericytoma, display variably prominent adipocytes and occasional myxoid background as well as lipoblast-like cells that can lead to the wrong diagnosis of myxoid liposarcoma and benign lipomatous tumors [21].

Lipoblastoma is usually a well-circumscribed benign lipomatous tumor, morphologically resembling fetal adipose tissue. Most cases of lipoblastoma are present in infants under the age of 3 years, with 2:1 male predominance. Occasional cases have been reported in children up to 8 years. The majority of lipoblastomas are subcutaneous, lobulated, and slowly growing. The rare cases of deep-seated, often intramuscular and diffusely infiltrative lipoblastomas are designated as lipoblastomatosis.

Smears from lipoblastoma are composed of variable, but usually large, clusters, and tissue fragments of small to moderately sized adipocytes with vacuolated cytoplasm and round uniform nuclei in a myxoid background matrix. Tumor tissue fragments often contain branching capillaries of middle size, similar to regular lipomas (Figs. 5.16 and 5.17). Areas of regular adipocytes and hibernoma-like cells, as well as uni- or multi-vacuolated lipoblast-like cells in the sheets of lipoblastomas, are common findings (Table 5.3).

Genetic rearrangement of chromosome region 8q11-13 involving the PLAG1 gene has been reported in a majority of cases. Gene fusions HAS2-PLAG1 and COL1A2-PLAG1 result in up-regulation of PLAG1 that activates transcription [22]. FISH, PCR, and NGS can detect these genetic changes on fresh or fixed material. Gain of chromosome 8 has also been noted, and can be detected with cytogenetics [23].

Myxoid liposarcoma and regular lipoma constitute differential diagnoses of lipoblastoma in FNA smears. Both lipoma and myxoid liposarcoma occur in older patient populations than does lipoblastoma. In addition, lipoblastomas lack the branching capillary network seen in smears from myxoid liposarcoma, and most lipomas lack the prominent myxoid background of a lipoblastoma.

Lipoblastoma is a lobular tumor composed of a mixture of mature and immature fat cells in varying proportions. A myxoid stroma, lipoblast-like cells, primitive spindle-shaped mesenchymal cells, and capillaries are typical features of histological sections in immature areas of lipoblastoma. The more mature component resembles a common lipoma with occasional hibernoma-like cells. Single cases of FNA of lipoblastoma have been published to date [24–34].

Lipoblastoma may mature toward a common lipoma, and the characteristic immature areas may be very small and focal. This is a common problem in the obtaining of diagnostic specimens by FNA.

Fibrous hamartoma of infancy (FHI) is a rare, benign, superficial, and usually solitary tumor composed of a mixture of mature adipose tissue, septa, and bands of fibrous tissue with hypo cellular areas alternating with fascicles of fibroblasts/myofibroblasts and nests of small primitive round-to-ovoid and spindled cells in a basophilic, myxoid matrix. FHI occurs in infants and children up to 2 years of age, but approximately 25% of cases are congenital. FHI is very rare in older children. Males are affected predominantly. Typical sites include deep dermis and subcutaneous tissue of the trunk (axilla, upper back), shoulders, and groin/perineum. The size is variable but usually does not exceed 5 cm. The histogenesis of FHI is unclear. The clinical course is typically benign and the prognosis excellent.

Smears of fibrous hamartoma of infancy show variable cellularity and are composed of small sheets and clusters of bland fibroblastic spindle cells with an admixture of dispersed spindle cells and fragments of mature adipose tissue (Figs. 5.18, 5.19, and 5.20). Myxoid and collagenous matrix may be part of aspiration smears, but mitotic figures and necrosis are absent (Table 5.4).

Fibroblastic/myofibroblastic component typically expresses SMA and rarely desmin. S-100 protein positivity occurs in the mature adipose tissue, and variable CD34, and often positive CD31 reactivity, in immature mesenchymal and pseudoangiomatous foci. β-catenin is negative.

Very few cases have been analyzed cytogenetically, but complex translocations have been described and illustrated with FISH [35].

Infantile fibrosarcoma constitutes differential diagnosis of FHI in FNA smears. Most cases of congenital fibrosarcoma arise in the extremities and yield hypercellular smears containing clusters, often compact, of slightly atypical spindle cells with scanty cytoplasm and hyperchromatic nuclei with coarse chromatin pattern. Compared to those, smears of FHI are moderately or sparse cellular with bland spindle component with an admixture of mature fat.

Diagnosis of FHI is made by histological examination to identify the characteristic triphasic pattern consisting of fibrous spindle cells delimiting islands of mature fat and primitive spindle cells. Apart from single case reports [36–38], there appear to be few descriptions of the FNA features of this lesion [9, 39, 40].

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive, low-grade fibroblastic neoplasm arising most often in young and middle-aged adults, but may be seen in all ages, including patients in the pediatric age group. DFSP is a superficial neoplasm involving both dermis and subcutis of trunk, proximal extremities, and groin, but may occasionally occur elsewhere in the body. In rare cases, DFSP also involves superficial soft tissue. The clinical history is often long with a slowly growing tumor, over a period of 5 years or more. This relatively rare neoplasm (less than 1% of all sarcomas) tends to recur locally in up to 50% of cases but has no metastatic potential. Rare cases of recurrent and sometimes also primary DFSP can progress to fibrosarcomatous (high-grade) DFSP, which can show an aggressive clinical course including metastases in about 10–15% of cases. The tumors referred for FNA are almost exclusively exophytic-nodular.

The most frequent type of smear is richly cellular with dense spindle cell clusters embedded in a collagen/fibrillar and occasionally myxoid matrix admixed with loosely clustered and dissociated spindle cells or naked nuclei (Figs. 5.21 and 5.22). The proportion of cell clusters and dissociated cells is variable, but in some smears these can be approximately equal. A storiform growth pattern is observed in cell clusters and sheets in the majority of cases. Tumor cells have poorly defined cytoplasmic borders and relatively uniform, spindle shaped or oval nuclei. Spindle cells with a better defined cytoplasm show bipolar cytoplasmic processes, but a majority of dispersed cells have poorly preserved cytoplasm, or lacked cytoplasm completely. The nuclei are basophilic fusiform, ovoid or round, showing a mild anisokaryosis, fine and homogeneous chromatin, and inconspicuous nucleoli (Fig. 5.23). Somewhat coarser chromatin and mild pleomorphism are usually seen in a minor component of smears, and need not be associated with the fibrosarcomatous variety of DFSP (Table 5.5).

Tumor cells of DFSP stain strongly for CD34 and express occasionally aberrant weak staining for EMA. Fibrosarcomatous variant of DFSP may show loss of CD34 positivity and increased positivity of TP53.

Supernumerary ring chromosomes with material derived from chromosomes 17 and 22 are a common finding, and a translocation t(17,22)(q21;q13) can be found in the majority of cases using FISH and PCR [41]. Both the translocation and the ring chromosome result in a fusion gene COL1A1-PDGFB, which stimulates cell growth and tumor development [42, 43]. FISH, SNP array, and NGS can be used for evaluation on fresh or fixed material.

The morphologic appearance of smears from DFSP can be similar to other spindle cell lesions—both benign and locally aggressive and malignant—such as benign fibrous histiocytoma, SFT, nodular fasciitis , neurofibroma, perineurioma, low-grade fibromyxoid sarcoma, monophasic synovial sarcoma, and fibrosarcoma. The most important differential diagnosis is cellular benign fibrous histiocytoma. The presence of histiocytes and/or giant cells favors histiocytoma. Furthermore the spindle cells in fibrous histiocytoma are CD34 negative a in majority of cases, and only occasionally display weak focal immunoreactivity for CD34. Many of the spindle cell tumors that are differentials of DFSP have at least certain characteristic clinical and morphological features, such as the anatomical location and rate of growth, which helps to distinguish them from DFSP. Ancillary techniques—cell block sections and immunocytochemistry—are of great importance in differentiating DFSP from other, particularly malignant, spindle cell neoplasms. Cell block sections facilitate storiform architecture and a characteristic pattern of fat infiltration. DFSP usually expresses a strong positivity for CD34, which together with a lack of immunoreactivity for keratins, EMA, MUC4 and S-100 protein, helps to exclude monophasic synovial sarcoma, low-grade fibromyxoid sarcoma, and nerve sheath tumors (Figs. 5.24 and 5.25). Positivity for CD34 can create some confusion when differentiating DFSP from SFT, since SFT also expresses CD34 positivity. However, SFT expresses STAT6 and the clinical characteristics, and usually the routine microscopic examination, can help in making a correct diagnosis.

Many studies have addressed histopathology, but only three series and a few case reports describing the cytological features of DFSP exist [44–57]. The 14 cases from Curie Institute [48] and 14 cases from Lund University Hospital [50] analyzed in this thesis are by far the largest series in the literature, allowing a better-founded cytomorphological analysis of this entity. The conclusions of these two studies are similar. Cytomorphological features of FNA smears alone are not sufficiently characteristic to permit a confident histotype diagnosis of DFSP. Cellular smears from DFSP are most often considered as low-grade malignant spindle cell sarcoma. Cell block sections facilitate a definitive subtype diagnosis, which requires also the confirmatory CD34 positivity [9, 56].

Smears of the fibrosarcomatous variant of DFSP display mild-to-moderate pleomorphism and occasional hyperchromatic nuclei with coarser chromatin, but examination of FNA smears alone gives no help in differentiating DFSP from its high-grade fibrosarcomatous counterpart.

Angiomatoid fibrous histiocytoma (AFH) is an indolent, rarely metastasizing neoplasm of uncertain lineage, commonly arising in the deep dermis and subcutaneous tissue of the extremities in children and young adults with a median age of 14 years. AFH may rarely occur in adults and affect other sites such as lung or bone. Enzinger in 1979 first designated the tumor as angiomatoid malignant fibrous histiocytoma. The tumor was later renamed angiomatoid fibrous histiocytoma because of its slow growth and rare metastasis. AFH is a rare neoplasm, accounting for approximately 0.3% of all soft tissue neoplasms, albeit incidence may be underestimated as clinically, the tumor is often mistaken for hematoma or hemangioma. AFH commonly presents as a partly cystic mass with hemorrhage, and FNA smears are bloody and show variable cellularity with ovoid-to-spindled histiocytoid cells that may be isolated or in clusters. Some of these cells are slightly atypical and may contain hemosiderin.

Most tumors are asymptomatic, with no indication of pain or any external sensation. Local symptoms, such as pain or tenderness, are extremely rare, and general symptoms of anemia, weight loss, and fever are observed in a minority of cases.

Local recurrence has been reported in 11% of patients and distant metastasis in 1%; wide excision is recommended as the treatment of AFH.

The cytomorphologic features are mostly non-distinctive and include cellular smears with ovoid-to-spindled histiocytoid cells that may be isolated or in clusters and, in almost all cases, in a bloody background, but rarely with lymphoplasmacytic infiltrate (Figs. 5.26, 5.27, and 5.28). The tumor cells showed mild-to-moderate anisokaryosis, often with nucleolus and vast, fragile wispy cytoplasm. Some of these cells are slightly atypical and others contain intracytoplasmic hemosiderin, and occasionally sheets and clusters of hemosiderin loaded histiocytoid cells are distinctive findings of FNA smears. Large cellular clusters with a capillary structure and a whorled arrangement of tumor cells and a fibroblast-like spindle- to-ovoid cell population can be appreciated in some cases (Table 5.6).